rs148766287

Variant names:

• chr21-45984508-C-G
• rs148766287
• NM_001848.3:c.428+39C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-45984508-C-G
• chr21-45984508-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001848.3(COL6A1):​c.428+39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,588,504 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (13 hom., cov: 35)
  • Exomes 𝑓: 0.013 (180 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.211

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-45984508-C-G is Benign according to our data. Variant chr21-45984508-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 93874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-45984508-C-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00942 (1436/152370) while in subpopulation NFE AF= 0.0146 (995/68038). AF 95% confidence interval is 0.0139. There are 13 homozygotes in gnomad4. There are 709 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.428+39C>G		intron_variant	Intron 3 of 34	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.428+39C>G		intron_variant	Intron 3 of 34	1	NM_001848.3	ENSP00000355180.3

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1439 AN: 152252 Hom.: 13 Cov.: 35

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.0105 AC: 2439 AN: 233246 Hom.: 28 AF XY: 0.0105 AC XY: 1345 AN XY: 128176

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00274

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00271

Gnomad FIN exome AF: 0.0215

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0121

GnomAD4 exome AF: 0.0132 AC: 18981 AN: 1436134 Hom.: 180 Cov.: 30 AF XY: 0.0129 AC XY: 9204 AN XY: 715584

Gnomad4 AFR exome AF: 0.00214

Gnomad4 AMR exome AF: 0.00271

Gnomad4 ASJ exome AF: 0.00288

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00942 AC: 1436 AN: 152370 Hom.: 13 Cov.: 35 AF XY: 0.00952 AC XY: 709 AN XY: 74506

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00539 Hom.: 2

Bravo AF: 0.00807

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 05, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Aug 03, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.40

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: rs148766287; hg19: chr21-47404422;