8-30679706-CTTTTTT-CTTTTT

Variant names:

• chr8-30679706-CT-C
• rs10715710
• NM_000637.5:c.1420-38delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000637.5(GSR):​c.1420-38delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (34898 hom., cov: 0)
  • Exomes 𝑓: 0.48 (10737 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 8-30679706-CT-C is Benign according to our data. Variant chr8-30679706-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1271483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 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.1420-38delA		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1333-38delA		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.1261-38delA		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.1420-38delA		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1333-38delA		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.1261-38delA		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 97055 AN: 134786 Hom.: 34909 Cov.: 0

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.770

GnomAD2 exomes AF: 0.487 AC: 64083 AN: 131578 AF XY: 0.487

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.493

Gnomad EAS exome AF: 0.499

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.488

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.480 AC: 558290 AN: 1162070 Hom.: 10737 Cov.: 0 AF XY: 0.480 AC XY: 279887 AN XY: 582832

African (AFR) AF: 0.450 AC: 11986 AN: 26608

American (AMR) AF: 0.478 AC: 16053 AN: 33562

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 10607 AN: 21848

East Asian (EAS) AF: 0.491 AC: 15857 AN: 32312

South Asian (SAS) AF: 0.478 AC: 35168 AN: 73566

European-Finnish (FIN) AF: 0.462 AC: 17568 AN: 37988

Middle Eastern (MID) AF: 0.479 AC: 1681 AN: 3512

European-Non Finnish (NFE) AF: 0.482 AC: 426088 AN: 883996

Other (OTH) AF: 0.478 AC: 23282 AN: 48678

GnomAD4 genome AF: 0.720 AC: 97039 AN: 134786 Hom.: 34898 Cov.: 0 AF XY: 0.719 AC XY: 46667 AN XY: 64884

African (AFR) AF: 0.616 AC: 22832 AN: 37040

American (AMR) AF: 0.758 AC: 9965 AN: 13154

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2625 AN: 3220

East Asian (EAS) AF: 0.888 AC: 4064 AN: 4576

South Asian (SAS) AF: 0.701 AC: 2907 AN: 4144

European-Finnish (FIN) AF: 0.740 AC: 5439 AN: 7352

Middle Eastern (MID) AF: 0.804 AC: 209 AN: 260

European-Non Finnish (NFE) AF: 0.754 AC: 47015 AN: 62344

Other (OTH) AF: 0.766 AC: 1410 AN: 1840

Alfa AF: 0.449 Hom.: 959

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
PhyloP100		-1.3
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: rs10715710; hg19: chr8-30537223;