3-130394792-T-G

Position:

• chr3-130394792-T-G

Variant summary

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

The NM_001278298.2(COL6A5):​c.2993-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 806,690 control chromosomes in the GnomAD database, including 32,992 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 0.29 (7342 hom., cov: 32)
  • Exomes 𝑓: 0.25 (25650 hom.)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

Genes affected

COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A5	NM_001278298.2	c.2993-98T>G		intron_variant		ENST00000373157.9	NP_001265227.1
COL6A5	NM_153264.7	c.2993-98T>G		intron_variant			NP_694996.5
COL6A5	NR_022012.3	n.3331-98T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A5	ENST00000373157.9	c.2993-98T>G		intron_variant		2	NM_001278298.2	ENSP00000362250	P2
COL6A5	ENST00000312481.11	c.2993-98T>G		intron_variant, NMD_transcript_variant		1		ENSP00000309762
COL6A5	ENST00000512836.6	c.2993-98T>G		intron_variant		2		ENSP00000422898	A2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43896 AN: 151986 Hom.: 7316 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.252 AC: 164968 AN: 654586 Hom.: 25650 AF XY: 0.254 AC XY: 86642 AN XY: 340626

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.673

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.289 AC: 43973 AN: 152104 Hom.: 7342 Cov.: 32 AF XY: 0.292 AC XY: 21744 AN XY: 74350

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.289

Alfa AF: 0.224 Hom.: 8661

Bravo AF: 0.311

Asia WGS AF: 0.486 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.92

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: rs10934938; hg19: chr3-130113635;