rs4925

chr10-104263031-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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 (★). 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 criteria provided, single submitter 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 -14 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 criteria_provided_single_submitter, 1 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	UniProt
GSTO1	NM_004832.3	c.419C>A	p.Ala140Asp	missense_variant	4/6	ENST00000369713.10
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
GSTO1	NM_001191002.2	c.367-3053C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10	c.419C>A	p.Ala140Asp	missense_variant	4/6	1	NM_004832.3	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: criteria provided, single submitter

Submissions by phenotype

GSTO1-related disorder Benign:1

Benign, criteria provided, single submitter

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
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
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;