rs156429
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
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
NM_002510.3 intron
Scores
2
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]
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ACMG classification
Classification made for transcript
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: 79830AN: 151984Hom.: 24498 Cov.: 32
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GnomAD4 exome AF: 0.404 AC: 309300AN: 765350Hom.: 66106 Cov.: 10 AF XY: 0.402 AC XY: 159737AN XY: 397718
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GnomAD4 genome AF: 0.526 AC: 79947AN: 152102Hom.: 24559 Cov.: 32 AF XY: 0.519 AC XY: 38571AN XY: 74340
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at