7-23246890-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002510.3(GPNMB):c.33G>A(p.Leu11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,613,964 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 4 hom. )
Consequence
GPNMB
NM_002510.3 synonymous
NM_002510.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.60
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 7-23246890-G-A is Benign according to our data. Variant chr7-23246890-G-A is described in ClinVar as [Benign]. Clinvar id is 718620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00359 (547/152256) while in subpopulation AFR AF= 0.0119 (494/41546). AF 95% confidence interval is 0.011. There are 2 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPNMB | NM_002510.3 | c.33G>A | p.Leu11= | synonymous_variant | 1/11 | ENST00000258733.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPNMB | ENST00000258733.9 | c.33G>A | p.Leu11= | synonymous_variant | 1/11 | 1 | NM_002510.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00358 AC: 545AN: 152138Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000867 AC: 218AN: 251492Hom.: 2 AF XY: 0.000714 AC XY: 97AN XY: 135922
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GnomAD4 exome AF: 0.000354 AC: 518AN: 1461708Hom.: 4 Cov.: 30 AF XY: 0.000285 AC XY: 207AN XY: 727186
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2018 | - - |
GPNMB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2019 | 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
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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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