Variant rs117330552 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.1823-31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,595,018 control chromosomes in the GnomAD database, including 1,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 75 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1211 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.36

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=-0.77).

BP6

Variant 21-46001222-C-T is Benign according to our data. Variant chr21-46001222-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46001222-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0262 (3993/152282) while in subpopulation NFE AF= 0.0441 (2996/67974). AF 95% confidence interval is 0.0428. There are 75 homozygotes in gnomad4. There are 1794 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 75 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3 linkuse as main transcript	c.1823-31C>T		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
COL6A1	ENST00000361866.8 linkuse as main transcript	c.1823-31C>T	intron_variant		1	NM_001848.3	P1
COL6A1	ENST00000498614.5 linkuse as main transcript	n.26C>T	non_coding_transcript_exon_variant	1/6	1
COL6A1	ENST00000463060.6 linkuse as main transcript	n.222-31C>T	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3994

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00663

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0302

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0441

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0266

AC:

6263

AN:

235740

Hom.:

134

AF XY:

0.0269

AC XY:

3471

AN XY:

128986

show subpopulations

Gnomad AFR exome

AF:

0.00749

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0342

Gnomad NFE exome

AF:

0.0428

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0370

AC:

53417

AN:

1442736

Hom.:

1211

Cov.:

AF XY:

0.0363

AC XY:

26050

AN XY:

716954

show subpopulations

Gnomad4 AFR exome

AF:

0.00552

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0369

Gnomad4 NFE exome

AF:

0.0434

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.0262

AC:

3993

AN:

152282

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1794

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00661

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.0302

Gnomad4 NFE

AF:

0.0441

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0338

Hom.:

Bravo

AF:

0.0245

Asia WGS

AF:

0.00636

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 05, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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