chr1-109661254-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000850.5(GSTM4):c.657A>G(p.Ter219=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 101 hom. )
Failed GnomAD Quality Control
Consequence
GSTM4
NM_000850.5 stop_retained
NM_000850.5 stop_retained
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.419
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 1-109661254-A-G is Benign according to our data. Variant chr1-109661254-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2858562.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.419 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GSTM4 | NM_000850.5 | c.657A>G | p.Ter219= | stop_retained_variant | 8/8 | ENST00000369836.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GSTM4 | ENST00000369836.9 | c.657A>G | p.Ter219= | stop_retained_variant | 8/8 | 1 | NM_000850.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 417AN: 143058Hom.: 3 Cov.: 32 FAILED QC
GnomAD3 genomes
?
AF:
AC:
417
AN:
143058
Hom.:
Cov.:
32
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000361 AC: 90AN: 248984Hom.: 20 AF XY: 0.000363 AC XY: 49AN XY: 134830
GnomAD3 exomes
AF:
AC:
90
AN:
248984
Hom.:
AF XY:
AC XY:
49
AN XY:
134830
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000418 AC: 602AN: 1440950Hom.: 101 Cov.: 31 AF XY: 0.000403 AC XY: 289AN XY: 717656
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
602
AN:
1440950
Hom.:
Cov.:
31
AF XY:
AC XY:
289
AN XY:
717656
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00291 AC: 417AN: 143176Hom.: 3 Cov.: 32 AF XY: 0.00292 AC XY: 205AN XY: 70224
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
417
AN:
143176
Hom.:
Cov.:
32
AF XY:
AC XY:
205
AN XY:
70224
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at