rs373948031

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_001848.3(COL6A1):​c.993C>T​(p.Asp331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,074,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

COL6A1
NM_001848.3 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.569
Variant links:
Genes affected
COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 21-45990413-C-T is Benign according to our data. Variant chr21-45990413-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258312.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.569 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL6A1NM_001848.3 linkuse as main transcriptc.993C>T p.Asp331= synonymous_variant 13/35 ENST00000361866.8 NP_001839.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A1ENST00000361866.8 linkuse as main transcriptc.993C>T p.Asp331= synonymous_variant 13/351 NM_001848.3 ENSP00000355180 P1

Frequencies

GnomAD3 genomes
AF:
0.000589
AC:
10
AN:
16968
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000713
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00262
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000117
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000836
AC:
17
AN:
203458
Hom.:
1
AF XY:
0.0000891
AC XY:
10
AN XY:
112296
show subpopulations
Gnomad AFR exome
AF:
0.000850
Gnomad AMR exome
AF:
0.000115
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000893
Gnomad SAS exome
AF:
0.0000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000105
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000501
AC:
53
AN:
1057032
Hom.:
0
Cov.:
49
AF XY:
0.0000465
AC XY:
24
AN XY:
516504
show subpopulations
Gnomad4 AFR exome
AF:
0.000268
Gnomad4 AMR exome
AF:
0.000168
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000285
Gnomad4 SAS exome
AF:
0.0000814
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000818
GnomAD4 genome
AF:
0.000588
AC:
10
AN:
17000
Hom.:
0
Cov.:
0
AF XY:
0.000986
AC XY:
8
AN XY:
8114
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.000709
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00260
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000117
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000862
Hom.:
0
Bravo
AF:
0.000170

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Aug 17, 2015- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 06, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
2.3
DANN
Benign
0.93

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: rs373948031; hg19: chr21-47410327; COSMIC: COSV62613001; COSMIC: COSV62613001; API