NM_001855.5:c.139A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001855.5(COL15A1):c.139A>G(p.Ile47Val) variant causes a missense change. The variant allele was found at a frequency of 0.00254 in 1,614,180 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 48 hom. )

Consequence

COL15A1
NM_001855.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.76

Publications

4 publications found

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005355954).

BP6

Variant 9-98985603-A-G is Benign according to our data. Variant chr9-98985603-A-G is described in ClinVar as [Benign]. Clinvar id is 3056690.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (2043/152352) while in subpopulation AFR AF = 0.047 (1952/41570). AF 95% confidence interval is 0.0452. There are 50 homozygotes in GnomAd4. There are 950 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL15A1	NM_001855.5 link	c.139A>G	p.Ile47Val	missense_variant	Exon 3 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.139A>G	p.Ile47Val	missense_variant	Exon 3 of 42	1	NM_001855.5	ENSP00000364140.3		P39059
COL15A1	ENST00000471477.1 link	n.562A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2037

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00355

AC:

891

AN:

251074

AF XY:

0.00254

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00140

AC:

2052

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

917

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0496

AC:

1659

AN:

33480

American (AMR)

AF:

0.00219

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000197

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

1111966

Other (OTH)

AF:

0.00295

AC:

178

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0134

AC:

2043

AN:

152352

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

950

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0470

AC:

1952

AN:

41570

American (AMR)

AF:

0.00411

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68032

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

214

320

427

534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.0155

ESP6500AA

AF:

0.0474

AC:

209

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00460

AC:

559

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COL15A1-related disorder

Benign:1

Mar 12, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.050

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.0

L;.

PhyloP100

3.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.59

N;.

REVEL

Benign

0.067

Sift

Benign

0.20

T;.

Sift4G

Benign

0.10

T;T

Polyphen

0.15

B;.

Vest4

0.10

MVP

0.44

MPC

0.23

ClinPred

0.031

GERP RS

1.5

Varity_R

0.033

gMVP

0.23

Mutation Taster

=98/2

polymorphism

(source)

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

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NM_001855.5:c.139A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over