chr8-30679706-CTTTT-C

Variant names:

• chr8-30679706-CTTTT-C
• rs10715710
• NM_000637.5:c.1420-41_1420-38delAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000637.5(GSR):​c.1420-41_1420-38delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,299,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSR	NM_000637.5	c.1420-41_1420-38delAAAA		intron_variant	Intron 12 of 12	ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.1420-41_1420-38delAAAA		intron_variant	Intron 12 of 12	1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.0000519 AC: 7 AN: 134844 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000760

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000321

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00104 AC: 137 AN: 131578 Hom.: 0 AF XY: 0.00105 AC XY: 76 AN XY: 72352

Gnomad AFR exome AF: 0.000758

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.000470

Gnomad EAS exome AF: 0.000766

Gnomad SAS exome AF: 0.000372

Gnomad FIN exome AF: 0.00161

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.000576

GnomAD4 exome AF: 0.00104 AC: 1207 AN: 1164810 Hom.: 0 AF XY: 0.000947 AC XY: 554 AN XY: 584716

Gnomad4 AFR exome AF: 0.000781

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.000715

Gnomad4 SAS exome AF: 0.000335

Gnomad4 FIN exome AF: 0.000866

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.0000519 AC: 7 AN: 134844 Hom.: 0 Cov.: 0 AF XY: 0.0000617 AC XY: 4 AN XY: 64880

Gnomad4 AFR AF: 0.0000540

Gnomad4 AMR AF: 0.0000760

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000218

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000137

Gnomad4 NFE AF: 0.0000321

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00143 Hom.: 959

ClinVar

Not reported in ClinVar

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;