9-99003559-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001855.5(COL15A1):c.1172C>T(p.Thr391Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,552,182 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0031 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 88 hom. )

Consequence

COL15A1
NM_001855.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.571

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025786161).

BP6

Variant 9-99003559-C-T is Benign according to our data. Variant chr9-99003559-C-T is described in ClinVar as [Benign]. Clinvar id is 708044.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL15A1	NM_001855.5 link	c.1172C>T	p.Thr391Met	missense_variant	Exon 8 of 42	ENST00000375001.8	NP_001846.3	P39059B3KTP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL15A1	ENST00000375001.8 link	c.1172C>T	p.Thr391Met	missense_variant	Exon 8 of 42	1	NM_001855.5	ENSP00000364140.3		P39059

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

482

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0811

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00569

AC:

1190

AN:

209128

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.000145

Gnomad AMR exome

AF:

0.000193

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0820

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000304

Gnomad OTH exome

AF:

0.00338

GnomAD4 exome

AF:

0.00190

AC:

2663

AN:

1399838

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1295

AN XY:

694858

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30732

American (AMR)

AF:

0.000277

AC:

AN:

36088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24248

East Asian (EAS)

AF:

0.0595

AC:

2120

AN:

35648

South Asian (SAS)

AF:

0.00235

AC:

182

AN:

77392

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52252

Middle Eastern (MID)

AF:

0.000360

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

1080438

Other (OTH)

AF:

0.00532

AC:

306

AN:

57484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00314

AC:

478

AN:

152344

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

261

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41590

American (AMR)

AF:

0.000914

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0805

AC:

416

AN:

5168

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68040

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00367

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00646

AC:

784

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

COL15A1-related disorder

Benign:1

Jun 13, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

not provided

Benign:1

Dec 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.039

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.9

L;.

PhyloP100

0.57

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;.

Sift4G

Benign

0.10

T;T

Polyphen

0.97

D;.

Vest4

0.16

MVP

0.73

MPC

0.083

ClinPred

0.010

GERP RS

1.9

Varity_R

0.032

gMVP

0.17

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Loading publications...

9-99003559-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over