rs1002149

Variant names:

• chr8-30728221-G-T
• rs1002149
• ENST00000896917.1:c.-386C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-30728221-G-T
• chr8-30728221-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000896917.1(GSR):​c.-386C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,046 control chromosomes in the GnomAD database, including 3,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3195 hom., cov: 32)
• Consequence: GSR ENST00000896917.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.34
• Publications: 29 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-30728221-G-T is Benign according to our data. Variant chr8-30728221-G-T is described in ClinVar as Benign. ClinVar VariationId is 1276408.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000896917.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSR	ENST00000896917.1		c.-386C>A		upstream_gene	N/A	ENSP00000566976.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30198 AN: 151928 Hom.: 3190 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.199 AC: 30236 AN: 152046 Hom.: 3195 Cov.: 32 AF XY: 0.201 AC XY: 14956 AN XY: 74326

African (AFR) AF: 0.254 AC: 10534 AN: 41472

American (AMR) AF: 0.187 AC: 2859 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 571 AN: 3472

East Asian (EAS) AF: 0.156 AC: 803 AN: 5144

South Asian (SAS) AF: 0.298 AC: 1439 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1968 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11544 AN: 67964

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.178 Hom.: 8812

Bravo AF: 0.196

Asia WGS AF: 0.210 AC: 732 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.67
PhyloP100		-2.3
PromoterAI		-0.016	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1002149; hg19: chr8-30585738;