NM_001848.3:c.13C>G

Variant names:

• chr21-45981863-C-G
• rs1235513102
• NM_001848.3:c.13C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001848.3(COL6A1):​c.13C>G​(p.Arg5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,441,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: COL6A1 NM_001848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 0 publications found

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]

COL6A1 Gene-Disease associations (from GenCC):

• Bethlem myopathy 1A

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
• collagen 6-related myopathy

  Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• Ullrich congenital muscular dystrophy 1A

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05520007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	NM_001848.3	MANE Select	c.13C>G	p.Arg5Gly	missense	Exon 1 of 35	NP_001839.2	P12109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.13C>G	p.Arg5Gly	missense	Exon 1 of 35	ENSP00000355180.3	P12109
	COL6A1	ENST00000866134.1		c.13C>G	p.Arg5Gly	missense	Exon 1 of 7	ENSP00000536193.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000555 AC: 8 AN: 1441226 Hom.: 0 Cov.: 33 AF XY: 0.00000559 AC XY: 4 AN XY: 715560

African (AFR) AF: 0.00 AC: 0 AN: 32966

American (AMR) AF: 0.00 AC: 0 AN: 42682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 38346

South Asian (SAS) AF: 0.00 AC: 0 AN: 83014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4574

European-Non Finnish (NFE) AF: 0.00000725 AC: 8 AN: 1104084

Other (OTH) AF: 0.00 AC: 0 AN: 59444

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.5
DANN	Benign	0.30
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.11
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.16
Sift	Benign	0.52	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.39		Loss of MoRF binding (P = 5e-04)
MVP		0.25
MPC		0.28
ClinPred		0.015	T
GERP RS		-4.9
PromoterAI		0.011	Neutral
Varity_R		0.079
gMVP		0.44
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1235513102; hg19: chr21-47401777;