8-30682454-A-T

Position:

• chr8-30682454-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000221130.11(GSR):​c.1154-393T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,216 control chromosomes in the GnomAD database, including 48,896 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 0.80 (48896 hom., cov: 34)
• Consequence: GSR ENST00000221130.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.1154-393T>A		intron_variant		ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.1154-393T>A		intron_variant		1	NM_000637.5	ENSP00000221130	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121710 AN: 152098 Hom.: 48850 Cov.: 34

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.800 AC: 121812 AN: 152216 Hom.: 48896 Cov.: 34 AF XY: 0.799 AC XY: 59499 AN XY: 74422

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.829

Alfa AF: 0.777 Hom.: 5734

Bravo AF: 0.809

Asia WGS AF: 0.821 AC: 2854 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	11
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2911678; hg19: chr8-30539971;