8-30679706-CT-C

Variant summary

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

The NM_000637.5(GSR):c.1420-38del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (34898 hom., cov: 0)
  • Exomes 𝑓: 0.48 (10737 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

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-CT-C is Benign according to our data. Variant chr8-30679706-CT-C is described in ClinVar as [Benign]. Clinvar id is 1271483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.720 AC: 97055 AN: 134786 Hom.: 34909 Cov.: 0

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.770

GnomAD3 exomes AF: 0.487 AC: 64083 AN: 131578 Hom.: 1375 AF XY: 0.487 AC XY: 35202 AN XY: 72352

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.493

Gnomad EAS exome AF: 0.499

Gnomad SAS exome AF: 0.479

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.488

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.480 AC: 558290 AN: 1162070 Hom.: 10737 Cov.: 0 AF XY: 0.480 AC XY: 279887 AN XY: 582832

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.720 AC: 97039 AN: 134786 Hom.: 34898 Cov.: 0 AF XY: 0.719 AC XY: 46667 AN XY: 64884

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.766

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

- -

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;