8-30689449-G-C

Position:

• chr8-30689449-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000637.5(GSR):​c.883-130C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 798,170 control chromosomes in the GnomAD database, including 238,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43669 hom., cov: 31)
  • Exomes 𝑓: 0.77 (194629 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 8-30689449-G-C is Benign according to our data. Variant chr8-30689449-G-C is described in ClinVar as [Benign]. Clinvar id is 1286141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.883-130C>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.883-130C>G		intron_variant		1	NM_000637.5	ENSP00000221130	P1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114770 AN: 151864 Hom.: 43647 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.774 AC: 500213 AN: 646188 Hom.: 194629 AF XY: 0.770 AC XY: 266471 AN XY: 346010

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.809

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.756 AC: 114840 AN: 151982 Hom.: 43669 Cov.: 31 AF XY: 0.757 AC XY: 56224 AN XY: 74276

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.795

Alfa AF: 0.750 Hom.: 5073

Bravo AF: 0.759

Asia WGS AF: 0.788 AC: 2737 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.57

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: rs2253409; hg19: chr8-30546966;