rs2850175

Positions:

• chr21-45994974-A-C
• chr21-45994974-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001848.3(COL6A1):​c.1398+745A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,328 control chromosomes in the GnomAD database, including 58,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58828 hom., cov: 35)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A1	NM_001848.3	c.1398+745A>C		intron_variant		ENST00000361866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A1	ENST00000361866.8	c.1398+745A>C		intron_variant		1	NM_001848.3	P1
COL6A1	ENST00000683550.1	n.173+745A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133629 AN: 152210 Hom.: 58765 Cov.: 35

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.850

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.878 AC: 133748 AN: 152328 Hom.: 58828 Cov.: 35 AF XY: 0.877 AC XY: 65331 AN XY: 74480

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.849

Alfa AF: 0.861 Hom.: 2768

Bravo AF: 0.883

Asia WGS AF: 0.815 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs2850175; hg19: chr21-47414888;