rs4925

Positions:

• chr10-104263031-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004832.3(GSTO1):​c.419C>A​(p.Ala140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,519,098 control chromosomes in the GnomAD database, including 58,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4921 hom., cov: 33)
  • Exomes 𝑓: 0.27 (54027 hom.)
• Consequence: GSTO1 NM_004832.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.992

Genes affected

GSTO1 (HGNC:13312): (glutathione S-transferase omega 1) The protein encoded by this gene is an omega class glutathione S-transferase (GST) with glutathione-dependent thiol transferase and dehydroascorbate reductase activities. GSTs are involved in the metabolism of xenobiotics and carcinogens. The encoded protein acts as a homodimer and is found in the cytoplasm. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

LOC124902497 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015232861).
• BP6: Variant 10-104263031-C-A is Benign according to our data. Variant chr10-104263031-C-A is described in ClinVar as [Benign]. Clinvar id is 3059603.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTO1	NM_004832.3	c.419C>A	p.Ala140Asp	missense_variant	4/6	ENST00000369713.10	NP_004823.1
LOC124902497	XR_007062284.1	n.365+5522G>T		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191003.2	c.335C>A	p.Ala112Asp	missense_variant	4/6		NP_001177932.1
GSTO1	NM_001191002.2	c.367-3053C>A		intron_variant			NP_001177931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTO1	ENST00000369713.10	c.419C>A	p.Ala140Asp	missense_variant	4/6	1	NM_004832.3	ENSP00000358727	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35883 AN: 152060 Hom.: 4920 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.274

GnomAD3 exomes AF: 0.248 AC: 60720 AN: 245134 Hom.: 8488 AF XY: 0.254 AC XY: 33683 AN XY: 132524

Gnomad AFR exome AF: 0.0976

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.135

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.310

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.272 AC: 372389 AN: 1366918 Hom.: 54027 Cov.: 24 AF XY: 0.273 AC XY: 186857 AN XY: 684390

Gnomad4 AFR exome AF: 0.0884

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.236 AC: 35893 AN: 152180 Hom.: 4921 Cov.: 33 AF XY: 0.233 AC XY: 17319 AN XY: 74390

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.271

Alfa AF: 0.301 Hom.: 18522

Bravo AF: 0.229

TwinsUK AF: 0.313 AC: 1162

ALSPAC AF: 0.314 AC: 1212

ESP6500AA AF: 0.109 AC: 481

ESP6500EA AF: 0.310 AC: 2665

ExAC AF: 0.252 AC: 30562

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GSTO1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.022	.;T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.73	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.49	.;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Benign	0.053
Sift	Uncertain	0.015	D;D;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.23	.;B;.
Vest4		0.11
MPC		0.24
ClinPred		0.0080	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.51

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

Other links and lift over

dbSNP: rs4925; hg19: chr10-106022789; COSMIC: COSV63846494; COSMIC: COSV63846494;