8-30717423-G-C

Variant names:

• chr8-30717423-G-C
• rs2978296
• NM_000637.5:c.307-5335C>G

Variant summary

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

The NM_000637.5(GSR):​c.307-5335C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,990 control chromosomes in the GnomAD database, including 46,590 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 0.78 (46590 hom., cov: 30)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	NM_000637.5	MANE Select	c.307-5335C>G		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.307-5335C>G		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.307-5335C>G		intron	N/A	NP_001182032.1	P00390-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	ENST00000221130.11	TSL:1 MANE Select	c.307-5335C>G		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.307-5335C>G		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.307-5335C>G		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118662 AN: 151872 Hom.: 46554 Cov.: 30

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.781 AC: 118746 AN: 151990 Hom.: 46590 Cov.: 30 AF XY: 0.778 AC XY: 57806 AN XY: 74286

African (AFR) AF: 0.715 AC: 29624 AN: 41456

American (AMR) AF: 0.791 AC: 12082 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2910 AN: 3468

East Asian (EAS) AF: 0.863 AC: 4446 AN: 5152

South Asian (SAS) AF: 0.691 AC: 3333 AN: 4820

European-Finnish (FIN) AF: 0.777 AC: 8202 AN: 10552

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55444 AN: 67962

Other (OTH) AF: 0.796 AC: 1679 AN: 2108

Alfa AF: 0.785 Hom.: 5865

Bravo AF: 0.784

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.67
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: rs2978296; hg19: chr8-30574940;