21-45996410-C-T

Variant names:

• chr21-45996410-C-T
• rs9978314
• NM_001848.3:c.1399-1011C>T

Variant summary

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

The NM_001848.3(COL6A1):​c.1399-1011C>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 152,112 control chromosomes in the GnomAD database, including 20,939 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 0.52 (20939 hom., cov: 33)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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 (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.1399-1011C>T		intron_variant	Intron 20 of 34	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.1399-1011C>T		intron_variant	Intron 20 of 34	1	NM_001848.3	ENSP00000355180.3
COL6A1	ENST00000683550.1	n.174-1011C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78659 AN: 151994 Hom.: 20915 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.518 AC: 78729 AN: 152112 Hom.: 20939 Cov.: 33 AF XY: 0.512 AC XY: 38049 AN XY: 74354

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.478

Alfa AF: 0.489 Hom.: 15831

Bravo AF: 0.520

Asia WGS AF: 0.307 AC: 1071 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	0.92
DANN	Benign	0.63

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: rs9978314; hg19: chr21-47416324;