NM_017617.5(NOTCH1):c.4656G>A (p.Ala1552=) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Jan 2, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003987549.1

Allele description [Variation Report for NM_017617.5(NOTCH1):c.4656G>A (p.Ala1552=)]

NM_017617.5(NOTCH1):c.4656G>A (p.Ala1552=)

Gene:

NOTCH1:notch receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.3

Genomic location:

Preferred name:

NM_017617.5(NOTCH1):c.4656G>A (p.Ala1552=)

HGVS:

NC_000009.12:g.136505035C>T
NG_007458.1:g.45752G>A
NM_017617.5:c.4656G>AMANE SELECT
NP_060087.3:p.Ala1552=
LRG_1122t1:c.4656G>A
LRG_1122:g.45752G>A
LRG_1122p1:p.Ala1552=
NC_000009.11:g.139399487C>T
NM_017617.3:c.4656G>A

Links:

dbSNP: rs375091696

NCBI 1000 Genomes Browser:

rs375091696

Molecular consequence:

NM_017617.5:c.4656G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004803496	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jan 2, 2024)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 24943832, 16614245, 21670202, 22210878, 19635999, 26837699, 23086750, 19245433, 22077063, 15472075, 23734977, 22858860 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004803496

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Jan 2, 2024)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

Baliakas P, Hadzidimitriou A, Sutton LA, Rossi D, Minga E, Villamor N, Larrayoz M, Kminkova J, Agathangelidis A, Davis Z, Tausch E, Stalika E, Kantorova B, Mansouri L, Scarfò L, Cortese D, Navrkalova V, Rose-Zerilli MJ, Smedby KE, Juliusson G, Anagnostopoulos A, Makris AM, et al.

Leukemia. 2015 Feb;29(2):329-36. doi: 10.1038/leu.2014.196. Epub 2014 Jun 19.

PubMed [citation]

PMID:: 24943832

Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia.

Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig WD, Tolle G, Happich M, Muckenthaler MU, Kulozik AE.

Blood. 2006 Aug 15;108(4):1151-7. Epub 2006 Apr 13.

PubMed [citation]

PMID:: 16614245

See all PubMed Citations (12)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004803496.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

Variant summary: NOTCH1 c.4656G>A alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.8e-05 in 239224 control chromosomes. The observed variant frequency is approximately 140.45 fold of the estimated maximal expected allele frequency for a pathogenic variant in NOTCH1 causing Adams-Oliver Syndrome 5 phenotype (6.3e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4656G>A in individuals affected with Adams-Oliver Syndrome 5 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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