Variant 7-23256914-G-A 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.390G>A(p.Pro130Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,612,572 control chromosomes in the GnomAD database, including 128,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13432 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115373 hom. )

Consequence

GPNMB
NM_002510.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.551

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=-0.85).

BP6

Variant 7-23256914-G-A is Benign according to our data. Variant chr7-23256914-G-A is described in ClinVar as [Benign]. Clinvar id is 3059129.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.551 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPNMB	NM_002510.3 link	c.390G>A	p.Pro130Pro	synonymous_variant	Exon 4 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.390G>A	p.Pro130Pro	synonymous_variant	Exon 4 of 11	1	NM_002510.3	ENSP00000258733.5		Q14956-2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62963

AN:

152028

Hom.:

13423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.363

AC:

91234

AN:

251092

Hom.:

17657

AF XY:

0.369

AC XY:

50028

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.393

AC:

574575

AN:

1460426

Hom.:

115373

Cov.:

AF XY:

0.393

AC XY:

285465

AN XY:

726578

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.271

Gnomad4 ASJ exome

AF:

0.425

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.414

AC:

63010

AN:

152146

Hom.:

13432

Cov.:

AF XY:

0.410

AC XY:

30481

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.490

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.438

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.435

Alfa

AF:

0.410

Hom.:

18930

Bravo

AF:

0.415

Asia WGS

AF:

0.330

AC:

1148

AN:

3478

EpiCase

AF:

0.415

EpiControl

AF:

0.409

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPNMB-related disorder

Benign:1

Oct 23, 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

-0.85

CADD

Benign

0.16

DANN

Benign

0.70

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