rs3594

Variant names:

• chr8-30678143-C-A
• rs3594
• NM_000637.5:c.*1377G>T

Variant summary

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

The NM_000637.5(GSR):​c.*1377G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,696 control chromosomes in the GnomAD database, including 8,105 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 0.32 (8105 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: GSR NM_000637.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 27 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSR	NM_000637.5	c.*1377G>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000221130.11	NP_000628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11	c.*1377G>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_000637.5	ENSP00000221130.5
GSR	ENST00000643653.1	n.*2660G>T		downstream_gene_variant				ENSP00000494854.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47925 AN: 151578 Hom.: 8106 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.324

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.316 AC: 47923 AN: 151696 Hom.: 8105 Cov.: 31 AF XY: 0.319 AC XY: 23644 AN XY: 74128

African (AFR) AF: 0.177 AC: 7330 AN: 41424

American (AMR) AF: 0.294 AC: 4468 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1226 AN: 5152

South Asian (SAS) AF: 0.379 AC: 1825 AN: 4814

European-Finnish (FIN) AF: 0.463 AC: 4829 AN: 10436

Middle Eastern (MID) AF: 0.372 AC: 108 AN: 290

European-Non Finnish (NFE) AF: 0.378 AC: 25667 AN: 67910

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.354 Hom.: 21406

Bravo AF: 0.298

Asia WGS AF: 0.307 AC: 1062 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs3594; hg19: chr8-30535660;