8-30682106-T-G

Position:

• chr8-30682106-T-G

Variant summary

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

The ENST00000221130.11(GSR):​c.1154-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,559,624 control chromosomes in the GnomAD database, including 466,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42298 hom., cov: 33)
  • Exomes 𝑓: 0.78 (424011 hom.)
• Consequence: GSR ENST00000221130.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.384

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-30682106-T-G is Benign according to our data. Variant chr8-30682106-T-G is described in ClinVar as [Benign]. Clinvar id is 1272685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSR	NM_000637.5	c.1154-45A>C		intron_variant		ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.1154-45A>C		intron_variant		1	NM_000637.5	ENSP00000221130.5

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112785 AN: 151930 Hom.: 42283 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.790

GnomAD3 exomes AF: 0.779 AC: 194531 AN: 249684 Hom.: 76214 AF XY: 0.779 AC XY: 105460 AN XY: 135416

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.833

Gnomad EAS exome AF: 0.902

Gnomad SAS exome AF: 0.730

Gnomad FIN exome AF: 0.773

Gnomad NFE exome AF: 0.780

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.775 AC: 1091384 AN: 1407576 Hom.: 424011 Cov.: 22 AF XY: 0.774 AC XY: 544387 AN XY: 703504

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.742 AC: 112850 AN: 152048 Hom.: 42298 Cov.: 33 AF XY: 0.744 AC XY: 55269 AN XY: 74328

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.787

Alfa AF: 0.755 Hom.: 10586

Bravo AF: 0.743

Asia WGS AF: 0.801 AC: 2784 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.54

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: rs2250192; hg19: chr8-30539623;