8-30703370-C-T

Position:

• chr8-30703370-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000637.5(GSR):​c.493-130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 898,928 control chromosomes in the GnomAD database, including 126,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (17466 hom., cov: 32)
  • Exomes 𝑓: 0.53 (108847 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-30703370-C-T is Benign according to our data. Variant chr8-30703370-C-T is described in ClinVar as [Benign]. Clinvar id is 1267009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSR	NM_000637.5	c.493-130G>A		intron_variant		ENST00000221130.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSR	ENST00000221130.11	c.493-130G>A		intron_variant		1	NM_000637.5	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68058 AN: 151918 Hom.: 17467 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.532 AC: 397565 AN: 746892 Hom.: 108847 AF XY: 0.532 AC XY: 208955 AN XY: 392990

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.448 AC: 68063 AN: 152036 Hom.: 17466 Cov.: 32 AF XY: 0.453 AC XY: 33645 AN XY: 74310

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.462

Alfa AF: 0.536 Hom.: 29719

Bravo AF: 0.428

Asia WGS AF: 0.430 AC: 1496 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.031
DANN	Benign	0.56

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: rs3779647; hg19: chr8-30560887;