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rs4988235

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005915.6(MCM6):c.1917+326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,102 control chromosomes in the GnomAD database, including 17,494 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 ( 17494 hom., cov: 32)

Consequence

MCM6
NM_005915.6 intron

Scores

2

Clinical Significance

association no assertion criteria provided O:2

Conservation

PhyloP100: 0.00800
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCM6NM_005915.6 linkuse as main transcriptc.1917+326C>T intron_variant ENST00000264156.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCM6ENST00000264156.3 linkuse as main transcriptc.1917+326C>T intron_variant 1 NM_005915.6 P1
MCM6ENST00000483902.1 linkuse as main transcriptn.544+326C>T intron_variant, non_coding_transcript_variant 2
MCM6ENST00000492091.1 linkuse as main transcriptn.343+326C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.397
AC:
60370
AN:
151984
Hom.:
17499
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.121
Gnomad AMI
AF:
0.768
Gnomad AMR
AF:
0.228
Gnomad ASJ
AF:
0.130
Gnomad EAS
AF:
0.00212
Gnomad SAS
AF:
0.163
Gnomad FIN
AF:
0.577
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.635
Gnomad OTH
AF:
0.294
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.397
AC:
60356
AN:
152102
Hom.:
17494
Cov.:
32
AF XY:
0.381
AC XY:
28329
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.121
Gnomad4 AMR
AF:
0.227
Gnomad4 ASJ
AF:
0.130
Gnomad4 EAS
AF:
0.00212
Gnomad4 SAS
AF:
0.163
Gnomad4 FIN
AF:
0.577
Gnomad4 NFE
AF:
0.635
Gnomad4 OTH
AF:
0.291
Alfa
AF:
0.505
Hom.:
24250
Bravo
AF:
0.359
Asia WGS
AF:
0.0730
AC:
255
AN:
3478

ClinVar

Significance: association
Submissions summary: Other:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Lactase persistence Other:2
association, no assertion criteria providedliterature onlyOMIMJan 26, 2021- -
association, no assertion criteria providedreference populationiDNA Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
13
Dann
Benign
0.91

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4988235; hg19: chr2-136608646; API