rs16827446

chr3-130413358-C-T

Variant summary

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

The NM_001278298.2(COL6A5):c.4663-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 151,746 control chromosomes in the GnomAD database, including 791 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 0.084 (791 hom., cov: 32)
• Consequence: COL6A5 NM_001278298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A5	NM_001278298.2	c.4663-187C>T		intron_variant		ENST00000373157.9
COL6A5	NM_153264.7	c.4663-187C>T		intron_variant
COL6A5	NR_022012.3	n.5001-187C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A5	ENST00000373157.9	c.4663-187C>T		intron_variant		2	NM_001278298.2	P2
COL6A5	ENST00000312481.11	c.4663-187C>T		intron_variant, NMD_transcript_variant		1
COL6A5	ENST00000512836.6	c.4663-187C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12728 AN: 151628 Hom.: 789 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.0840 AC: 12751 AN: 151746 Hom.: 791 Cov.: 32 AF XY: 0.0818 AC XY: 6064 AN XY: 74124

Gnomad4 AFR AF: 0.0862

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0911

Gnomad4 SAS AF: 0.0557

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.0925

Alfa AF: 0.0881 Hom.: 357

Bravo AF: 0.0896

Asia WGS AF: 0.0690 AC: 241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.35

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: rs16827446; hg19: chr3-130132202;