NM_001848.3:c.1822+42G>C

Variant names:

• chr21-46000809-G-C
• rs13053065
• NM_001848.3:c.1822+42G>C

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.1822+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,611,126 control chromosomes in the GnomAD database, including 75,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7972 hom., cov: 36)
  • Exomes 𝑓: 0.30 (67420 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.554

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 21-46000809-G-C is Benign according to our data. Variant chr21-46000809-G-C is described in ClinVar as [Benign]. Clinvar id is 93831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46000809-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A1	NM_001848.3	c.1822+42G>C		intron_variant	Intron 29 of 34	ENST00000361866.8	NP_001839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A1	ENST00000361866.8	c.1822+42G>C		intron_variant	Intron 29 of 34	1	NM_001848.3	ENSP00000355180.3
COL6A1	ENST00000466285.1	n.381G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
COL6A1	ENST00000463060.6	n.-122G>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48266 AN: 152094 Hom.: 7964 Cov.: 36

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.298

GnomAD3 exomes AF: 0.281 AC: 70527 AN: 250916 Hom.: 10444 AF XY: 0.276 AC XY: 37484 AN XY: 135730

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.300 AC: 438392 AN: 1458914 Hom.: 67420 Cov.: 36 AF XY: 0.297 AC XY: 215782 AN XY: 725956

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.317 AC: 48302 AN: 152212 Hom.: 7972 Cov.: 36 AF XY: 0.317 AC XY: 23550 AN XY: 74402

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.294

Alfa AF: 0.213 Hom.: 650

Bravo AF: 0.325

Asia WGS AF: 0.177 AC: 620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs13053065; hg19: chr21-47420723; COSMIC: COSV62613519; COSMIC: COSV62613519;