8-30689449-G-C

Variant names:

• chr8-30689449-G-C
• rs2253409
• NM_000637.5:c.883-130C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000637.5(GSR):​c.883-130C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 798,170 control chromosomes in the GnomAD database, including 238,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43669 hom., cov: 31)
  • Exomes 𝑓: 0.77 (194629 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.00
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 8-30689449-G-C is Benign according to our data. Variant chr8-30689449-G-C is described in ClinVar as Benign. ClinVar VariationId is 1286141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 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.883-130C>G		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.796-130C>G		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.882+3520C>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.883-130C>G		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.796-130C>G		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.882+3520C>G		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114770 AN: 151864 Hom.: 43647 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.774 AC: 500213 AN: 646188 Hom.: 194629 AF XY: 0.770 AC XY: 266471 AN XY: 346010

African (AFR) AF: 0.675 AC: 11818 AN: 17496

American (AMR) AF: 0.804 AC: 28512 AN: 35456

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 16498 AN: 20388

East Asian (EAS) AF: 0.875 AC: 29624 AN: 33872

South Asian (SAS) AF: 0.696 AC: 45325 AN: 65134

European-Finnish (FIN) AF: 0.780 AC: 34215 AN: 43856

Middle Eastern (MID) AF: 0.790 AC: 2326 AN: 2944

European-Non Finnish (NFE) AF: 0.777 AC: 305794 AN: 393696

Other (OTH) AF: 0.783 AC: 26101 AN: 33346

GnomAD4 genome AF: 0.756 AC: 114840 AN: 151982 Hom.: 43669 Cov.: 31 AF XY: 0.757 AC XY: 56224 AN XY: 74276

African (AFR) AF: 0.683 AC: 28285 AN: 41418

American (AMR) AF: 0.790 AC: 12030 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2783 AN: 3466

East Asian (EAS) AF: 0.904 AC: 4680 AN: 5176

South Asian (SAS) AF: 0.684 AC: 3292 AN: 4814

European-Finnish (FIN) AF: 0.788 AC: 8323 AN: 10560

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52894 AN: 68004

Other (OTH) AF: 0.795 AC: 1677 AN: 2110

Alfa AF: 0.750 Hom.: 5073

Bravo AF: 0.759

Asia WGS AF: 0.788 AC: 2737 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.57
PhyloP100		-2.0
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: rs2253409; hg19: chr8-30546966;