VCV000007687.1 - ClinVar

NM_005915.6(MCM6):c.1917+226G>C

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.

(1)

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.

association

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005915.6(MCM6):c.1917+226G>C

Variation ID: 7687 Accession: VCV000007687.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q21.3 2: 135851176 (GRCh38) [ NCBI UCSC ] 2: 136608746 (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	Apr 4, 2013	Apr 4, 2013	Jun 16, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NM_005915.6:c.1917+226G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NC_000002.12:g.135851176C>G
NC_000002.11:g.136608746C>G
NG_008104.2:g.8994G>C
NG_008958.1:g.30266G>C
LRG_338:g.8994G>C

... more HGVS ... less HGVS

Protein change

Other names

IVS13, G/C

Canonical SPDI

NC_000002.12:135851175:C:G

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.

0.00339 (G)

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

Trans-Omics for Precision Medicine (TOPMed) 0.00006

1000 Genomes Project 30x 0.00265

1000 Genomes Project 0.00339

Links

ClinGen: CA212874 OMIM: 601806.0003 dbSNP: rs145946881 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 17159977 Fig. 1d to determine the location of this allele on the current reference sequence.

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.
MCM6		-	-	GRCh38 GRCh37	71	89

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.
Lactase persistence	association (1)	no assertion criteria provided	Jun 16, 2015	RCV000008126.2

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.
association (Jun 16, 2015)	no assertion criteria provided Method: literature only	LACTASE PERSISTENCE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000028331.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 17159977‚ 21327791 Comment on evidence: Among 40 individuals with lactase nonpersistence and 69 with lactase persistence all of East African origin, Tishkoff et al. (2007) found that a single-nucleotide polymorphism … (more) Among 40 individuals with lactase nonpersistence and 69 with lactase persistence all of East African origin, Tishkoff et al. (2007) found that a single-nucleotide polymorphism (SNP) in intron 13 of the MCM6 gene, G/C(-14010), showed a significant association with the lactase persistence trait (223100) in Kenyans (n = 53; chi square = 14.4, P = 0.0007) and Tanzanians (n = 31; chi square = 10.9; P = 0.0043). Genotyping of 123 SNPs across a 3-Mb region flanking the MCM6 and LCT (603202) genes in the full set of 470 individuals with reliable phenotype data and in 24 additional individuals confirmed the association. Analyses of transcriptional regulation of the LCT promoter in vitro indicated that otherwise identical constructs with a C(-14010) allele consistently produced approximately 18% more luciferase than constructs with the G(-14010) allele, an increase in transcription similar to that observed for the T(-13910) allele in Europeans (601806.0001). The authors estimated that the C(-14010) allele originated in African populations approximately 2,700 to 6,800 years ago. Jensen et al. (2011) stated that the G/C(-14010) SNP resides at the 5-prime end of a 450-bp sequence with LCT enhancer function. Using reporter gene assays with Caco2 cells, they found that the C allele had increased enhancer activity compared with the ancestral G allele. Sequence analysis and gel-shift assays identified functional OCT1- and HNF1-alpha (HNF1A; 142410)-binding sites flanking this SNP. OCT1 binding to the C allele was increased by HNF1-alpha occupancy. (less)

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
The -14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity.	Jensen TG	Human genetics	2011	PMID: 21327791
Convergent adaptation of human lactase persistence in Africa and Europe.	Tishkoff SA	Nature genetics	2007	PMID: 17159977

Text-mined citations for rs145946881 ...

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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_005915.6(MCM6):c.1917+226G>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs145946881 ...