Variant rs202231424 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001848.3(COL6A1):c.805-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00998 in 1,604,462 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 7 hom., cov: 33)

Exomes 𝑓: 0.010 ( 106 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.41

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]

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 21-45989048-G-A is Benign according to our data. Variant chr21-45989048-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00798 (1216/152302) while in subpopulation AMR AF= 0.0143 (219/15304). AF 95% confidence interval is 0.0128. There are 7 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.805-36G>A		intron_variant		ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8 linkuse as main transcript	c.805-36G>A		intron_variant		1	NM_001848.3	ENSP00000355180.3		P12109

Frequencies

GnomAD3 genomes

AF:

0.00799

AC:

1216

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00805

AC:

1964

AN:

244070

Hom.:

AF XY:

0.00763

AC XY:

1012

AN XY:

132648

show subpopulations

Gnomad AFR exome

AF:

0.00279

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.00507

Gnomad EAS exome

AF:

0.000277

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00353

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00876

GnomAD4 exome

AF:

0.0102

AC:

14799

AN:

1452160

Hom.:

106

Cov.:

AF XY:

0.00980

AC XY:

7072

AN XY:

721814

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.00550

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00472

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00798

AC:

1216

AN:

152302

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

561

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00836

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.16

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over