rs2236488

Positions:

• chr21-46002798-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001848.3(COL6A1):​c.2434+88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,407,794 control chromosomes in the GnomAD database, including 195,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19930 hom., cov: 33)
  • Exomes 𝑓: 0.52 (175285 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-46002798-C-T is Benign according to our data. Variant chr21-46002798-C-T is described in ClinVar as [Benign]. Clinvar id is 679199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46002798-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.2434+88C>T		intron_variant		ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.2434+88C>T		intron_variant		1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 76658 AN: 150186 Hom.: 19911 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.519 AC: 652694 AN: 1257494 Hom.: 175285 AF XY: 0.514 AC XY: 324022 AN XY: 629868

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.510 AC: 76714 AN: 150300 Hom.: 19930 Cov.: 33 AF XY: 0.506 AC XY: 37161 AN XY: 73418

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.465

Alfa AF: 0.521 Hom.: 1924

Bravo AF: 0.512

Asia WGS AF: 0.293 AC: 1016 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2236488; hg19: chr21-47422712; COSMIC: COSV62612817; COSMIC: COSV62612817;