rs156429

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002510.3(GPNMB):​c.1019-116T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 767,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

GPNMB
NM_002510.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPNMBNM_002510.3 linkc.1019-116T>A intron_variant Intron 6 of 10 ENST00000258733.9 NP_002501.1 Q14956-2Q96F58A0A024RA55

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPNMBENST00000258733.9 linkc.1019-116T>A intron_variant Intron 6 of 10 1 NM_002510.3 ENSP00000258733.5 Q14956-2
GPNMBENST00000381990.6 linkc.1019-80T>A intron_variant Intron 6 of 10 1 ENSP00000371420.2 Q14956-1
GPNMBENST00000647578.1 linkc.1103-116T>A intron_variant Intron 7 of 11 ENSP00000497362.1 A0A3B3ISS6
GPNMBENST00000479625.1 linkn.262T>A non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000521
AC:
4
AN:
767092
Hom.:
0
Cov.:
10
AF XY:
0.00000753
AC XY:
3
AN XY:
398582
show subpopulations
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
19256
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
29068
Gnomad4 ASJ exome
AF:
0.0000582
AC:
1
AN:
17184
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
35816
Gnomad4 SAS exome
AF:
0.0000171
AC:
1
AN:
58388
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
46840
Gnomad4 NFE exome
AF:
0.00000384
AC:
2
AN:
520170
Gnomad4 Remaining exome
AF:
0.00
AC:
0
AN:
36576
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.64
DANN
Benign
0.33

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.

Other links and lift over

dbSNP: rs156429; hg19: chr7-23306020; API