21-46000809-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001848.3(COL6A1):c.1822+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,611,126 control chromosomes in the GnomAD database, including 75,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7972 hom., cov: 36)

Exomes 𝑓: 0.30 ( 67420 hom. )

Consequence

COL6A1
NM_001848.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.554

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=-0.86).

BP6

Variant 21-46000809-G-C is Benign according to our data. Variant chr21-46000809-G-C is described in ClinVar as [Benign]. Clinvar id is 93831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46000809-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3 link	c.1822+42G>C		intron_variant	Intron 29 of 34	ENST00000361866.8	NP_001839.2	P12109A0A384P5H7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A1	ENST00000361866.8 link	c.1822+42G>C	intron_variant	Intron 29 of 34	1	NM_001848.3	ENSP00000355180.3	P12109
COL6A1	ENST00000466285.1 link	n.381G>C	non_coding_transcript_exon_variant	Exon 3 of 3	3
COL6A1	ENST00000463060.6 link	n.-122G>C	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48266

AN:

152094

Hom.:

7964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.281

AC:

70527

AN:

250916

Hom.:

10444

AF XY:

0.276

AC XY:

37484

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.300

AC:

438392

AN:

1458914

Hom.:

67420

Cov.:

AF XY:

0.297

AC XY:

215782

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.280

GnomAD4 genome

AF:

0.317

AC:

48302

AN:

152212

Hom.:

7972

Cov.:

AF XY:

0.317

AC XY:

23550

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.392

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.213

Hom.:

650

Bravo

AF:

0.325

Asia WGS

AF:

0.177

AC:

620

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.35

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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