rs3734431

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001512.4(GSTA4):​c.547-39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,538,188 control chromosomes in the GnomAD database, including 4,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 458 hom., cov: 32)
Exomes 𝑓: 0.076 ( 4167 hom. )

Consequence

GSTA4
NM_001512.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400
Variant links:
Genes affected
GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSTA4NM_001512.4 linkuse as main transcriptc.547-39T>C intron_variant ENST00000370963.9
GSTA4XM_005249035.5 linkuse as main transcriptc.547-39T>C intron_variant
GSTA4XM_011514534.4 linkuse as main transcriptc.436-39T>C intron_variant
GSTA4XM_011514535.4 linkuse as main transcriptc.436-39T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSTA4ENST00000370963.9 linkuse as main transcriptc.547-39T>C intron_variant 1 NM_001512.4 P1O15217-1

Frequencies

GnomAD3 genomes
AF:
0.0766
AC:
11650
AN:
152124
Hom.:
457
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0672
Gnomad AMI
AF:
0.0296
Gnomad AMR
AF:
0.0885
Gnomad ASJ
AF:
0.0920
Gnomad EAS
AF:
0.0643
Gnomad SAS
AF:
0.0822
Gnomad FIN
AF:
0.0484
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0839
Gnomad OTH
AF:
0.0844
GnomAD3 exomes
AF:
0.0778
AC:
17738
AN:
227940
Hom.:
758
AF XY:
0.0790
AC XY:
9751
AN XY:
123500
show subpopulations
Gnomad AFR exome
AF:
0.0656
Gnomad AMR exome
AF:
0.0715
Gnomad ASJ exome
AF:
0.0995
Gnomad EAS exome
AF:
0.0773
Gnomad SAS exome
AF:
0.0836
Gnomad FIN exome
AF:
0.0539
Gnomad NFE exome
AF:
0.0821
Gnomad OTH exome
AF:
0.0877
GnomAD4 exome
AF:
0.0761
AC:
105486
AN:
1385946
Hom.:
4167
Cov.:
22
AF XY:
0.0766
AC XY:
53016
AN XY:
692150
show subpopulations
Gnomad4 AFR exome
AF:
0.0654
Gnomad4 AMR exome
AF:
0.0710
Gnomad4 ASJ exome
AF:
0.0941
Gnomad4 EAS exome
AF:
0.0680
Gnomad4 SAS exome
AF:
0.0841
Gnomad4 FIN exome
AF:
0.0540
Gnomad4 NFE exome
AF:
0.0766
Gnomad4 OTH exome
AF:
0.0795
GnomAD4 genome
AF:
0.0766
AC:
11660
AN:
152242
Hom.:
458
Cov.:
32
AF XY:
0.0764
AC XY:
5691
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0674
Gnomad4 AMR
AF:
0.0884
Gnomad4 ASJ
AF:
0.0920
Gnomad4 EAS
AF:
0.0644
Gnomad4 SAS
AF:
0.0814
Gnomad4 FIN
AF:
0.0484
Gnomad4 NFE
AF:
0.0840
Gnomad4 OTH
AF:
0.0830
Alfa
AF:
0.0847
Hom.:
833
Bravo
AF:
0.0785
Asia WGS
AF:
0.0690
AC:
240
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.33
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs3734431; hg19: chr6-52843429; API