dbSNP rs8190996: GSR:c.696-10C>T (chr8-30696489-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000637.5(GSR):c.696-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,572,768 control chromosomes in the GnomAD database, including 160,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13723 hom., cov: 32)

Exomes 𝑓: 0.45 ( 146499 hom. )

Consequence

GSR
NM_000637.5 intron

Scores

Splicing: ADA: 0.00001487

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.367

Variant links:

Genes affected

GSR (HGNC:4623): (glutathione-disulfide reductase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]

GSR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 8-30696489-G-A is Benign according to our data. Variant chr8-30696489-G-A is described in ClinVar as [Benign]. Clinvar id is 439766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSR	NM_000637.5 link	c.696-10C>T		intron_variant	Intron 6 of 12	ENST00000221130.11	NP_000628.2	P00390-1V9HW90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11 link	c.696-10C>T		intron_variant	Intron 6 of 12	1	NM_000637.5	ENSP00000221130.5		P00390-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63293

AN:

151804

Hom.:

13717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.422

GnomAD3 exomes

AF:

0.452

AC:

113277

AN:

250774

Hom.:

26228

AF XY:

0.454

AC XY:

61519

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.477

Gnomad SAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.575

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.444

GnomAD4 exome

AF:

0.452

AC:

642387

AN:

1420846

Hom.:

146499

Cov.:

AF XY:

0.452

AC XY:

320695

AN XY:

709648

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.569

Gnomad4 NFE exome

AF:

0.453

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.417

AC:

63324

AN:

151922

Hom.:

13723

Cov.:

AF XY:

0.421

AC XY:

31279

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.360

Gnomad4 EAS

AF:

0.474

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.432

Hom.:

23056

Bravo

AF:

0.402

Asia WGS

AF:

0.463

AC:

1610

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hemolytic anemia due to glutathione reductase deficiency

Benign:2

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GSR-related disorder

Benign:1

Mar 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.67

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over