rs201588451
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001481.3(GAS8):c.1221+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000746 in 1,593,706 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 2 hom. )
Consequence
GAS8
NM_001481.3 splice_donor_region, intron
NM_001481.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001395
2
Clinical Significance
Conservation
PhyloP100: 0.765
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]
URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]
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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 (BayesDel_noAF=-0.75).
BP6
Variant 16-90040513-G-A is Benign according to our data. Variant chr16-90040513-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00094 (143/152166) while in subpopulation AMR AF= 0.00295 (45/15280). AF 95% confidence interval is 0.00226. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAS8 | NM_001481.3 | c.1221+4G>A | splice_donor_region_variant, intron_variant | ENST00000268699.9 | |||
URAHP | NR_027335.2 | n.693-96C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAS8 | ENST00000268699.9 | c.1221+4G>A | splice_donor_region_variant, intron_variant | 1 | NM_001481.3 | P4 | |||
URAHP | ENST00000409873.5 | n.693-96C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000940 AC: 143AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000850 AC: 183AN: 215306Hom.: 1 AF XY: 0.000782 AC XY: 91AN XY: 116436
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GnomAD4 exome AF: 0.000726 AC: 1046AN: 1441540Hom.: 2 Cov.: 32 AF XY: 0.000741 AC XY: 530AN XY: 715530
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GnomAD4 genome AF: 0.000940 AC: 143AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000860 AC XY: 64AN XY: 74396
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
GAS8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 02, 2019 | 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). - |
Primary ciliary dyskinesia 33 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at