chr8-30679815-C-A

Position:

• chr8-30679815-C-A

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.1420-146G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 695,144 control chromosomes in the GnomAD database, including 14,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2728 hom., cov: 29)
  • Exomes 𝑓: 0.20 (11610 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 8-30679815-C-A is Benign according to our data. Variant chr8-30679815-C-A is described in ClinVar as [Benign]. Clinvar id is 1273497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.1420-146G>T		intron_variant		ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.1420-146G>T		intron_variant		1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27087 AN: 151140 Hom.: 2727 Cov.: 29

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.195 AC: 106086 AN: 543886 Hom.: 11610 AF XY: 0.192 AC XY: 56314 AN XY: 292980

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.179 AC: 27105 AN: 151258 Hom.: 2728 Cov.: 29 AF XY: 0.181 AC XY: 13320 AN XY: 73794

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.187

Alfa AF: 0.0779 Hom.: 115

Bravo AF: 0.184

Asia WGS AF: 0.254 AC: 882 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	-0.96
CADD	Benign	3.5
DANN	Benign	0.80

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: rs8191038; hg19: chr8-30537332;