rs41380347

Variant names:

• chr2-135851081-A-C
• rs41380347
• NM_005915.6:c.1917+321T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-135851081-A-C
• chr2-135851081-A-G
• chr2-135851081-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005915.6(MCM6):​c.1917+321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 152,322 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.00060 (8 hom., cov: 32)
• Consequence: MCM6 NM_005915.6 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.610
• Publications: 40 publications found

Genes affected

MCM6 (HGNC:6949): (minichromosome maintenance complex component 6) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Single nucleotide polymorphisms in the intron regions of this gene are associated with differential transcriptional activation of the promoter of the neighboring lactase gene and, thereby, influence lactose intolerance in early adulthood. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS2: High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM6	NM_005915.6	c.1917+321T>G		intron_variant	Intron 13 of 16	ENST00000264156.3	NP_005906.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM6	ENST00000264156.3	c.1917+321T>G		intron_variant	Intron 13 of 16	1	NM_005915.6	ENSP00000264156.2
MCM6	ENST00000483902.1	n.544+321T>G		intron_variant	Intron 1 of 1	2
MCM6	ENST00000492091.1	n.343+321T>G		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152204 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000597 AC: 91 AN: 152322 Hom.: 8 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74486

African (AFR) AF: 0.0000962 AC: 4 AN: 41588

American (AMR) AF: 0.00262 AC: 40 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.000357 Hom.: 0

Bravo AF: 0.000710

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

LACTASE PERSISTENCE Other:1

Nov 20, 2018

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41380347; hg19: chr2-136608651;