8-30679706-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000637.5(GSR):c.1420-39_1420-38del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,213,742 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 0)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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 -10 ACMG points.

• BP6: Variant 8-30679706-CTT-C is Benign according to our data. Variant chr8-30679706-CTT-C is described in ClinVar as [Benign]. Clinvar id is 1286961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSR	NM_000637.5	c.1420-39_1420-38del		intron_variant		ENST00000221130.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSR	ENST00000221130.11	c.1420-39_1420-38del		intron_variant		1	NM_000637.5	P1

Frequencies

GnomAD3 genomes AF: 0.00203 AC: 274 AN: 134800 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00297

Gnomad ASJ AF: 0.000932

Gnomad EAS AF: 0.00109

Gnomad SAS AF: 0.000240

Gnomad FIN AF: 0.00875

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.183 AC: 24102 AN: 131578 Hom.: 0 AF XY: 0.185 AC XY: 13402 AN XY: 72352

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.251

Gnomad SAS exome AF: 0.158

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.137 AC: 148300 AN: 1078942 Hom.: 0 AF XY: 0.138 AC XY: 74381 AN XY: 538252

Gnomad4 AFR exome AF: 0.0949

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.00204 AC: 275 AN: 134800 Hom.: 1 Cov.: 0 AF XY: 0.00239 AC XY: 155 AN XY: 64878

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00296

Gnomad4 ASJ AF: 0.000932

Gnomad4 EAS AF: 0.00109

Gnomad4 SAS AF: 0.000241

Gnomad4 FIN AF: 0.00875

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.00380

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs10715710; hg19: chr8-30537223;