chr8-30726387-C-T

Variant names:

• chr8-30726387-C-T
• rs8190893
• NM_000637.5:c.306+1143G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000637.5(GSR):​c.306+1143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,252 control chromosomes in the GnomAD database, including 164 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 0.041 (164 hom., cov: 32)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• hemolytic anemia due to glutathione reductase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000637.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	NM_000637.5	MANE Select	c.306+1143G>A		intron	N/A	NP_000628.2
	GSR	NM_001195102.3		c.306+1143G>A		intron	N/A	NP_001182031.1
	GSR	NM_001195103.3		c.306+1143G>A		intron	N/A	NP_001182032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	ENST00000221130.11	TSL:1 MANE Select	c.306+1143G>A		intron	N/A	ENSP00000221130.5
	GSR	ENST00000546342.5	TSL:1	c.306+1143G>A		intron	N/A	ENSP00000445516.1
	GSR	ENST00000541648.5	TSL:1	c.306+1143G>A		intron	N/A	ENSP00000444559.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6193 AN: 152134 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0407 AC: 6190 AN: 152252 Hom.: 164 Cov.: 32 AF XY: 0.0378 AC XY: 2817 AN XY: 74440

African (AFR) AF: 0.0127 AC: 526 AN: 41542

American (AMR) AF: 0.0385 AC: 589 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4832

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10610

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.0659 AC: 4481 AN: 68012

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0609 Hom.: 651

Bravo AF: 0.0420

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.0
DANN	Benign	0.88
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs8190893; hg19: chr8-30583904;