Variant chr3-130376649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001278298.2(COL6A5):c.480C>T(p.Asp160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,612,892 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 33 hom. )

Consequence

COL6A5
NM_001278298.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.38

Variant links:

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]

COL6A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-130376649-C-T is Benign according to our data. Variant chr3-130376649-C-T is described in ClinVar as [Benign]. Clinvar id is 771353.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.38 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1729/152214) while in subpopulation AFR AF= 0.0392 (1630/41538). AF 95% confidence interval is 0.0377. There are 29 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COL6A5	NM_001278298.2 linkuse as main transcript	c.480C>T	p.Asp160=	synonymous_variant	3/41	ENST00000373157.9
COL6A5	NM_153264.7 linkuse as main transcript	c.480C>T	p.Asp160=	synonymous_variant	3/40
COL6A5	NR_022012.3 linkuse as main transcript	n.818C>T		non_coding_transcript_exon_variant	3/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A5	ENST00000373157.9 linkuse as main transcript	c.480C>T	p.Asp160=	synonymous_variant	3/41	2	NM_001278298.2	P2
COL6A5	ENST00000312481.11 linkuse as main transcript	c.480C>T	p.Asp160=	synonymous_variant, NMD_transcript_variant	3/42	1			A8TX70-1
COL6A5	ENST00000512836.6 linkuse as main transcript	c.480C>T	p.Asp160=	synonymous_variant	3/40	2		A2	A8TX70-2

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1722

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00365

AC:

899

AN:

246362

Hom.:

AF XY:

0.00285

AC XY:

382

AN XY:

133838

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00680

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00132

AC:

1925

AN:

1460678

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

836

AN XY:

726550

show subpopulations

Gnomad4 AFR exome

AF:

0.0439

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.0114

AC:

1729

AN:

152214

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0392

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.95

DANN

Benign

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over