Variant 7-23246906-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002510.3(GPNMB):c.49T>C(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,584 control chromosomes in the GnomAD database, including 654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.034 ( 244 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 410 hom. )

Consequence

GPNMB
NM_002510.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.89

Variant links:

Genes affected

GPNMB (HGNC:4462): (glycoprotein nmb) The protein encoded by this gene is a type I transmembrane glycoprotein which shows homology to the pMEL17 precursor, a melanocyte-specific protein. GPNMB shows expression in the lowly metastatic human melanoma cell lines and xenografts but does not show expression in the highly metastatic cell lines. GPNMB may be involved in growth delay and reduction of metastatic potential. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GPNMB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-23246906-T-C is Benign according to our data. Variant chr7-23246906-T-C is described in ClinVar as [Benign]. Clinvar id is 3042316.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPNMB	NM_002510.3 link	c.49T>C	p.Leu17Leu	synonymous_variant	Exon 1 of 11	ENST00000258733.9	NP_002501.1	Q14956-2Q96F58A0A024RA55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPNMB	ENST00000258733.9 link	c.49T>C	p.Leu17Leu	synonymous_variant	Exon 1 of 11	1	NM_002510.3	ENSP00000258733.5		Q14956-2

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5102

AN:

152132

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0948

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.00893

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0191

AC:

4802

AN:

251492

Hom.:

234

AF XY:

0.0164

AC XY:

2230

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0968

Gnomad AMR exome

AF:

0.00705

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.00552

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00367

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00884

AC:

12913

AN:

1461334

Hom.:

410

Cov.:

AF XY:

0.00835

AC XY:

6068

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.0968

Gnomad4 AMR exome

AF:

0.00724

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0983

Gnomad4 SAS exome

AF:

0.00555

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00353

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0336

AC:

5114

AN:

152250

Hom.:

244

Cov.:

AF XY:

0.0335

AC XY:

2493

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0948

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.00894

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0376

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPNMB-related disorder

Benign:1

Mar 27, 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

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.41

DANN

Benign

0.42

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