8-30708428-C-T

Position:

• chr8-30708428-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000637.5(GSR):​c.423-287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,134 control chromosomes in the GnomAD database, including 23,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (23743 hom., cov: 33)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-30708428-C-T is Benign according to our data. Variant chr8-30708428-C-T is described in ClinVar as [Benign]. Clinvar id is 1258539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.423-287G>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.423-287G>A		intron_variant		1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81251 AN: 152016 Hom.: 23732 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.534 AC: 81286 AN: 152134 Hom.: 23743 Cov.: 33 AF XY: 0.542 AC XY: 40321 AN XY: 74364

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.533

Alfa AF: 0.618 Hom.: 59584

Bravo AF: 0.513

Asia WGS AF: 0.558 AC: 1940 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.46
DANN	Benign	0.31

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: rs2978663; hg19: chr8-30565945;