8-30717423-G-C

Position:

• chr8-30717423-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000637.5(GSR):​c.307-5335C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,990 control chromosomes in the GnomAD database, including 46,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46590 hom., cov: 30)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.307-5335C>G		intron_variant		ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.307-5335C>G		intron_variant		1	NM_000637.5	ENSP00000221130	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118662 AN: 151872 Hom.: 46554 Cov.: 30

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.797

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118746 AN: 151990 Hom.: 46590 Cov.: 30 AF XY: 0.778 AC XY: 57806 AN XY: 74286

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.796

Alfa AF: 0.785 Hom.: 5865

Bravo AF: 0.784

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.56

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: rs2978296; hg19: chr8-30574940;