8-30682454-A-T

Variant names:

• chr8-30682454-A-T
• rs2911678
• NM_000637.5:c.1154-393T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000637.5(GSR):​c.1154-393T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,216 control chromosomes in the GnomAD database, including 48,896 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 0.80 (48896 hom., cov: 34)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 10 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 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.1154-393T>A		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1067-393T>A		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.995-393T>A		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.1154-393T>A		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1067-393T>A		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.995-393T>A		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121710 AN: 152098 Hom.: 48850 Cov.: 34

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.800 AC: 121812 AN: 152216 Hom.: 48896 Cov.: 34 AF XY: 0.799 AC XY: 59499 AN XY: 74422

African (AFR) AF: 0.837 AC: 34768 AN: 41548

American (AMR) AF: 0.807 AC: 12336 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3472

East Asian (EAS) AF: 0.902 AC: 4676 AN: 5182

South Asian (SAS) AF: 0.729 AC: 3520 AN: 4828

European-Finnish (FIN) AF: 0.782 AC: 8280 AN: 10590

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52698 AN: 67994

Other (OTH) AF: 0.829 AC: 1753 AN: 2114

Alfa AF: 0.777 Hom.: 5734

Bravo AF: 0.809

Asia WGS AF: 0.821 AC: 2854 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	11
DANN	Benign	0.34
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2911678; hg19: chr8-30539971;