rs41283498
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000850.5(GSTM4):c.259+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00255 in 1,614,260 control chromosomes in the GnomAD database, including 9 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 8 hom. )
Consequence
GSTM4
NM_000850.5 splice_donor, intron
NM_000850.5 splice_donor, intron
Scores
3
3
1
Splicing: ADA: 1.000
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.39
Genes affected
GSTM4 (HGNC:4636): (glutathione S-transferase mu 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GSTM4 | NM_000850.5 | c.259+1G>A | splice_donor_variant, intron_variant | ENST00000369836.9 | NP_000841.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GSTM4 | ENST00000369836.9 | c.259+1G>A | splice_donor_variant, intron_variant | 1 | NM_000850.5 | ENSP00000358851.4 |
Frequencies
GnomAD3 genomes AF: 0.00159 AC: 242AN: 152250Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00181 AC: 456AN: 251490Hom.: 2 AF XY: 0.00185 AC XY: 252AN XY: 135916
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GnomAD4 exome AF: 0.00265 AC: 3868AN: 1461892Hom.: 8 Cov.: 32 AF XY: 0.00262 AC XY: 1908AN XY: 727248
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GnomAD4 genome AF: 0.00159 AC: 242AN: 152368Hom.: 1 Cov.: 32 AF XY: 0.00134 AC XY: 100AN XY: 74508
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -3
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at