rs41283498

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

Scores

3
3
1
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.39
Variant links:
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 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
GSTM4NM_000850.5 linkuse as main transcriptc.259+1G>A splice_donor_variant, intron_variant ENST00000369836.9 NP_000841.1 Q03013-1A0A140VKE3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GSTM4ENST00000369836.9 linkuse as main transcriptc.259+1G>A splice_donor_variant, intron_variant 1 NM_000850.5 ENSP00000358851.4 Q03013-1

Frequencies

GnomAD3 genomes
AF:
0.00159
AC:
242
AN:
152250
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000981
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00273
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00181
AC:
456
AN:
251490
Hom.:
2
AF XY:
0.00185
AC XY:
252
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.000520
Gnomad ASJ exome
AF:
0.00278
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000849
Gnomad FIN exome
AF:
0.00115
Gnomad NFE exome
AF:
0.00300
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00265
AC:
3868
AN:
1461892
Hom.:
8
Cov.:
32
AF XY:
0.00262
AC XY:
1908
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.000581
Gnomad4 ASJ exome
AF:
0.00314
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000881
Gnomad4 FIN exome
AF:
0.00165
Gnomad4 NFE exome
AF:
0.00309
Gnomad4 OTH exome
AF:
0.00225
GnomAD4 genome
AF:
0.00159
AC:
242
AN:
152368
Hom.:
1
Cov.:
32
AF XY:
0.00134
AC XY:
100
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.00273
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00286
Hom.:
0
Bravo
AF:
0.00159
TwinsUK
AF:
0.00270
AC:
10
ALSPAC
AF:
0.00415
AC:
16
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00384
AC:
33
ExAC
AF:
0.00166
AC:
201
EpiCase
AF:
0.00284
EpiControl
AF:
0.00207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
27
DANN
Uncertain
0.99
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Uncertain
0.97
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.30
Position offset: -3
DS_DL_spliceai
1.0
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41283498; hg19: chr1-110200294; API