rs2072699

Positions:

• chr21-45983414-G-A

Variant summary

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

The NM_001848.3(COL6A1):​c.227+651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 152,106 control chromosomes in the GnomAD database, including 129 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 0.016 (129 hom., cov: 31)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.227+651G>A		intron_variant		ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.227+651G>A		intron_variant		1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2418 AN: 151988 Hom.: 128 Cov.: 31

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0159 AC: 2421 AN: 152106 Hom.: 129 Cov.: 31 AF XY: 0.0178 AC XY: 1324 AN XY: 74368

Gnomad4 AFR AF: 0.00304

Gnomad4 AMR AF: 0.0604

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00773 Hom.: 6

Bravo AF: 0.0202

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.69

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: rs2072699; hg19: chr21-47403328;