chr8-30681905-T-A

Position:

• chr8-30681905-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000637.5(GSR):​c.1285+25A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,611,512 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (3 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.1285+25A>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.1285+25A>T		intron_variant		1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 230 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00138 AC: 347 AN: 251342 Hom.: 0 AF XY: 0.00141 AC XY: 192 AN XY: 135852

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00180 AC: 2630 AN: 1459302 Hom.: 3 Cov.: 30 AF XY: 0.00188 AC XY: 1363 AN XY: 726182

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00237

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000656

Gnomad4 NFE exome AF: 0.00213

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00151 AC: 230 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74430

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00168

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.78
DANN	Benign	0.70

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: rs200821383; hg19: chr8-30539422;