VCV000198044.74 - ClinVar

NM_000142.5(FGFR3):c.678C>T (p.Tyr226=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000142.5(FGFR3):c.678C>T (p.Tyr226=)

Variation ID: 198044 Accession: VCV000198044.74

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4p16.3 4: 1801682 (GRCh38) [ NCBI UCSC ] 4: 1803409 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 28, 2015	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000142.5:c.678C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000133.1:p.Tyr226=	synonymous
NM_001163213.2:c.678C>T	NP_001156685.1:p.Tyr226=	synonymous
NM_001354809.2:c.678C>T	NP_001341738.1:p.Tyr226=	synonymous
NM_001354810.2:c.678C>T	NP_001341739.1:p.Tyr226=	synonymous
NM_022965.4:c.678C>T	NP_075254.1:p.Tyr226=	synonymous
NR_148971.2:n.953C>T		non-coding transcript variant
NC_000004.12:g.1801682C>T
NC_000004.11:g.1803409C>T
NG_012632.1:g.13371C>T
LRG_1021:g.13371C>T
LRG_1021t1:c.678C>T	LRG_1021p1:p.Tyr226=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000004.12:1801681:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00040 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00040

1000 Genomes Project 30x 0.00078

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00100

The Genome Aggregation Database (gnomAD), exomes 0.00128

Exome Aggregation Consortium (ExAC) 0.00138

Trans-Omics for Precision Medicine (TOPMed) 0.00138

The Genome Aggregation Database (gnomAD) 0.00142

Links

ClinGen: CA203201 dbSNP: rs141575580 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FGFR3		No evidence available	No evidence available	GRCh38 GRCh37	983	1133

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (2)	criteria provided, single submitter	Apr 22, 2015	RCV000179257.13
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV001532499.41

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005263653.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Jun 22, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001783852.1 First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021
Benign (Nov 09, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002049653.2 First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024
Likely benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001748092.20 First in ClinVar: Jul 10, 2021 Last updated: Oct 20, 2024	Comment: FGFR3: BP4, BP7 Number of individuals with the variant: 6
Benign (Apr 22, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000231478.5 First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR3 Number of individuals with the variant: 1 Sex: mixed
Benign (Jan 18, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000762856.7 First in ClinVar: May 28, 2018 Last updated: Feb 20, 2024
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001969195.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001799955.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR3	-	-	-	-

Text-mined citations for rs141575580 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000142.5(FGFR3):c.678C>T (p.Tyr226=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs141575580 ...