rs139167960
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001481.3(GAS8):āc.841G>Cā(p.Asp281His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,614,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00060 ( 1 hom., cov: 33)
Exomes š: 0.00041 ( 1 hom. )
Consequence
GAS8
NM_001481.3 missense
NM_001481.3 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 7.20
Genes affected
GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.014992714).
BP6
Variant 16-90037316-G-C is Benign according to our data. Variant chr16-90037316-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 542273.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000597 (91/152332) while in subpopulation AMR AF= 0.00288 (44/15302). AF 95% confidence interval is 0.0022. There are 1 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GAS8 | NM_001481.3 | c.841G>C | p.Asp281His | missense_variant | 7/11 | ENST00000268699.9 | NP_001472.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GAS8 | ENST00000268699.9 | c.841G>C | p.Asp281His | missense_variant | 7/11 | 1 | NM_001481.3 | ENSP00000268699.4 |
Frequencies
GnomAD3 genomes AF: 0.000598 AC: 91AN: 152214Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000570 AC: 143AN: 250794Hom.: 0 AF XY: 0.000538 AC XY: 73AN XY: 135600
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GnomAD4 exome AF: 0.000409 AC: 598AN: 1461696Hom.: 1 Cov.: 31 AF XY: 0.000414 AC XY: 301AN XY: 727132
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GnomAD4 genome AF: 0.000597 AC: 91AN: 152332Hom.: 1 Cov.: 33 AF XY: 0.000564 AC XY: 42AN XY: 74488
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 33 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 06, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
GAS8-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
0.90
.;P;.
Vest4
MVP
MPC
0.082
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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