rs73868680

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001278298.2(COL6A5):c.7765G>A(p.Ala2589Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,468,390 control chromosomes in the GnomAD database, including 4,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 1208 hom., cov: 23)

Exomes 𝑓: 0.065 ( 3727 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.413

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006091118).

BP6

Variant 3-130471872-G-A is Benign according to our data. Variant chr3-130471872-G-A is described in ClinVar as [Benign]. Clinvar id is 402555.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COL6A5	NM_001278298.2 linkuse as main transcript	c.7765G>A	p.Ala2589Thr	missense_variant	40/41	ENST00000373157.9
COL6A5	NM_153264.7 linkuse as main transcript	c.7574+905G>A		intron_variant
COL6A5	NR_022012.3 linkuse as main transcript	n.8103G>A		non_coding_transcript_exon_variant	40/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A5	ENST00000373157.9 linkuse as main transcript	c.7765G>A	p.Ala2589Thr	missense_variant	40/41	2	NM_001278298.2	P2
COL6A5	ENST00000312481.11 linkuse as main transcript	c.7765G>A	p.Ala2589Thr	missense_variant, NMD_transcript_variant	40/42	1			A8TX70-1
COL6A5	ENST00000512482.1 linkuse as main transcript	c.1270G>A	p.Ala424Thr	missense_variant	5/6	5
COL6A5	ENST00000512836.6 linkuse as main transcript	c.7574+905G>A		intron_variant		2		A2	A8TX70-2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

15824

AN:

85468

Hom.:

1203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.0476

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.164

AC:

11817

AN:

72030

Hom.:

694

AF XY:

0.164

AC XY:

6330

AN XY:

38708

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0716

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.0461

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.0647

AC:

89457

AN:

1382786

Hom.:

3727

Cov.:

AF XY:

0.0657

AC XY:

44850

AN XY:

682376

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.0438

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0558

Gnomad4 OTH exome

AF:

0.0775

GnomAD4 genome

AF:

0.185

AC:

15859

AN:

85604

Hom.:

1208

Cov.:

AF XY:

0.180

AC XY:

7537

AN XY:

41830

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.0742

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.0476

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.0997

Hom.:

111

Bravo

AF:

0.116

ExAC

AF:

0.159

AC:

1354

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.45

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

REVEL

Benign

0.18

Sift4G

Uncertain

0.023

D;T;T

Vest4

0.080

MPC

0.051

ClinPred

0.0047

GERP RS

1.2

gMVP

0.054

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