rs17178299
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001481.3(GAS8):c.776G>A(p.Arg259Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0571 in 1,611,484 control chromosomes in the GnomAD database, including 3,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R259R) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.046 ( 216 hom., cov: 33)
Exomes 𝑓: 0.058 ( 2881 hom. )
Consequence
GAS8
NM_001481.3 missense
NM_001481.3 missense
Scores
6
10
Clinical Significance
Conservation
PhyloP100: 5.70
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0015008748).
BP6
?
Variant 16-90037251-G-A is Benign according to our data. Variant chr16-90037251-G-A is described in ClinVar as [Benign]. Clinvar id is 402892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAS8 | NM_001481.3 | c.776G>A | p.Arg259Gln | missense_variant | 7/11 | ENST00000268699.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAS8 | ENST00000268699.9 | c.776G>A | p.Arg259Gln | missense_variant | 7/11 | 1 | NM_001481.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0458 AC: 6962AN: 152128Hom.: 215 Cov.: 33
GnomAD3 genomes
?
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33
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GnomAD3 exomes AF: 0.0523 AC: 12981AN: 248434Hom.: 495 AF XY: 0.0511 AC XY: 6862AN XY: 134294
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GnomAD4 exome AF: 0.0582 AC: 84987AN: 1459238Hom.: 2881 Cov.: 31 AF XY: 0.0571 AC XY: 41409AN XY: 725666
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GnomAD4 genome ? AF: 0.0457 AC: 6960AN: 152246Hom.: 216 Cov.: 33 AF XY: 0.0458 AC XY: 3408AN XY: 74416
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261
ALSPAC
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241
ESP6500AA
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Primary ciliary dyskinesia 33 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
0.77
.;P;.
Vest4
MPC
0.022
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