Variant 9-98985952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001855.5(COL15A1):c.488G>A(p.Arg163His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,613,768 control chromosomes in the GnomAD database, including 26,767 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3664 hom., cov: 32)

Exomes 𝑓: 0.17 ( 23103 hom. )

Consequence

COL15A1
NM_001855.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

COL15A1 (HGNC:2192): (collagen type XV alpha 1 chain) This gene encodes the alpha chain of type XV collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Type XV collagen has a wide tissue distribution but the strongest expression is localized to basement membrane zones so it may function to adhere basement membranes to underlying connective tissue stroma. The proteolytically produced C-terminal fragment of type XV collagen is restin, a potentially antiangiogenic protein that is closely related to endostatin. Mouse studies have shown that collagen XV deficiency is associated with muscle and microvessel deterioration. [provided by RefSeq, May 2013]

COL15A1 links:

COL15A1 (HGNC:):

COL15A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022774637).

BP6

Variant 9-98985952-G-A is Benign according to our data. Variant chr9-98985952-G-A is described in ClinVar as [Benign]. Clinvar id is 3060205.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL15A1	NM_001855.5 linkuse as main transcript	c.488G>A	p.Arg163His	missense_variant	3/42	ENST00000375001.8	NP_001846.3	P39059B3KTP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL15A1	ENST00000375001.8 linkuse as main transcript	c.488G>A	p.Arg163His	missense_variant	3/42	1	NM_001855.5	ENSP00000364140.3	P39059
COL15A1	ENST00000610452.1 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	3/43	5			A0A087X0K0
COL15A1	ENST00000471477.1 linkuse as main transcript	n.911G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31473

AN:

151972

Hom.:

3655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.194

AC:

48874

AN:

251296

Hom.:

5490

AF XY:

0.190

AC XY:

25795

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.171

AC:

250001

AN:

1461678

Hom.:

23103

Cov.:

AF XY:

0.172

AC XY:

125118

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.207

AC:

31508

AN:

152090

Hom.:

3664

Cov.:

AF XY:

0.209

AC XY:

15540

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.163

Hom.:

4882

Bravo

AF:

0.219

TwinsUK

AF:

0.156

AC:

577

ALSPAC

AF:

0.149

AC:

575

ESP6500AA

AF:

0.315

AC:

1389

ESP6500EA

AF:

0.156

AC:

1339

ExAC

AF:

0.193

AC:

23436

Asia WGS

AF:

0.235

AC:

815

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COL15A1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.093

Sift

Benign

0.27

T;.

Sift4G

Benign

0.18

T;T

Polyphen

0.011

B;.

Vest4

0.21

MPC

0.090

ClinPred

0.0067

GERP RS

1.2

Varity_R

0.057

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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