rs156429

Positions:

• chr7-23266401-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002510.3(GPNMB):​c.1019-116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 917,452 control chromosomes in the GnomAD database, including 90,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (24559 hom., cov: 32)
  • Exomes 𝑓: 0.40 (66106 hom.)
• Consequence: GPNMB NM_002510.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPNMB	NM_002510.3	c.1019-116T>C		intron_variant		ENST00000258733.9	NP_002501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPNMB	ENST00000258733.9	c.1019-116T>C		intron_variant		1	NM_002510.3	ENSP00000258733.5
GPNMB	ENST00000381990.6	c.1019-80T>C		intron_variant		1		ENSP00000371420.2
GPNMB	ENST00000647578.1	c.1103-116T>C		intron_variant				ENSP00000497362.1
GPNMB	ENST00000479625.1	n.262T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79830 AN: 151984 Hom.: 24498 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.404 AC: 309300 AN: 765350 Hom.: 66106 Cov.: 10 AF XY: 0.402 AC XY: 159737 AN XY: 397718

Gnomad4 AFR exome AF: 0.882

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.526 AC: 79947 AN: 152102 Hom.: 24559 Cov.: 32 AF XY: 0.519 AC XY: 38571 AN XY: 74340

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.509

Alfa AF: 0.479 Hom.: 4002

Bravo AF: 0.541

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs156429; hg19: chr7-23306020; COSMIC: COSV51697980; COSMIC: COSV51697980;