8-30679706-CTTTTTT-CTT

Variant names:

• chr8-30679706-CTTTT-C
• rs10715710
• NM_000637.5:c.1420-41_1420-38delAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000637.5(GSR):​c.1420-41_1420-38delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,299,654 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.1420-41_1420-38delAAAA		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1333-41_1333-38delAAAA		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.1261-41_1261-38delAAAA		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.1420-41_1420-38delAAAA		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1333-41_1333-38delAAAA		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.1261-41_1261-38delAAAA		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.0000519 AC: 7 AN: 134844 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000760

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000218

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000321

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00104 AC: 137 AN: 131578 AF XY: 0.00105

Gnomad AFR exome AF: 0.000758

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.000470

Gnomad EAS exome AF: 0.000766

Gnomad FIN exome AF: 0.00161

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.000576

GnomAD4 exome AF: 0.00104 AC: 1207 AN: 1164810 Hom.: 0 AF XY: 0.000947 AC XY: 554 AN XY: 584716

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000781 AC: 21 AN: 26894

American (AMR) AF: 0.00107 AC: 36 AN: 33708

Ashkenazi Jewish (ASJ) AF: 0.00105 AC: 23 AN: 21850

East Asian (EAS) AF: 0.000715 AC: 23 AN: 32162

South Asian (SAS) AF: 0.000335 AC: 25 AN: 74716

European-Finnish (FIN) AF: 0.000866 AC: 33 AN: 38114

Middle Eastern (MID) AF: 0.000285 AC: 1 AN: 3512

European-Non Finnish (NFE) AF: 0.00111 AC: 982 AN: 885146

Other (OTH) AF: 0.00129 AC: 63 AN: 48708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000519 AC: 7 AN: 134844 Hom.: 0 Cov.: 0 AF XY: 0.0000617 AC XY: 4 AN XY: 64880

African (AFR) AF: 0.0000540 AC: 2 AN: 37032

American (AMR) AF: 0.0000760 AC: 1 AN: 13154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3220

East Asian (EAS) AF: 0.000218 AC: 1 AN: 4590

South Asian (SAS) AF: 0.00 AC: 0 AN: 4174

European-Finnish (FIN) AF: 0.000137 AC: 1 AN: 7324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000321 AC: 2 AN: 62380

Other (OTH) AF: 0.00 AC: 0 AN: 1830

Alfa AF: 0.00143 Hom.: 959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

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;