rs182549

chr2-135859184-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005915.6(MCM6):c.1362+117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 819,600 control chromosomes in the GnomAD database, including 143,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (17807 hom., cov: 32)
  • Exomes 𝑓: 0.56 (125432 hom.)
• Consequence: MCM6 NM_005915.6 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.140

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM6	NM_005915.6	c.1362+117G>A		intron_variant		ENST00000264156.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM6	ENST00000264156.3	c.1362+117G>A		intron_variant		1	NM_005915.6	P1
MCM6	ENST00000492091.1	n.181+3423G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.401 AC: 61022 AN: 152004 Hom.: 17812 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.557 AC: 371578 AN: 667478 Hom.: 125432 AF XY: 0.540 AC XY: 185644 AN XY: 343926

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.000582

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.401 AC: 61009 AN: 152122 Hom.: 17807 Cov.: 32 AF XY: 0.385 AC XY: 28658 AN XY: 74366

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.297

Alfa AF: 0.518 Hom.: 23705

Bravo AF: 0.363

Asia WGS AF: 0.0780 AC: 274 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Lactase persistence Other:1

association, no assertion criteria provided

literature only

OMIM

Jan 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.68
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs182549; hg19: chr2-136616754;