rs1542829

Positions:

• chr3-130418627-G-A

Variant summary

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

The NM_001278298.2(COL6A5):​c.4888-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0823 in 152,042 control chromosomes in the GnomAD database, including 614 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 0.082 (614 hom., cov: 31)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A5	NM_001278298.2	c.4888-242G>A		intron_variant		ENST00000373157.9
COL6A5	NM_153264.7	c.4888-242G>A		intron_variant
COL6A5	NR_022012.3	n.5226-242G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A5	ENST00000373157.9	c.4888-242G>A		intron_variant		2	NM_001278298.2	P2
COL6A5	ENST00000312481.11	c.4888-242G>A		intron_variant, NMD_transcript_variant		1
COL6A5	ENST00000512836.6	c.4888-242G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12489 AN: 151924 Hom.: 613 Cov.: 31

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0823 AC: 12511 AN: 152042 Hom.: 614 Cov.: 31 AF XY: 0.0839 AC XY: 6235 AN XY: 74328

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0640

Gnomad4 OTH AF: 0.0892

Alfa AF: 0.0719 Hom.: 922

Bravo AF: 0.0894

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.44

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: rs1542829; hg19: chr3-130137471;