8-30679706-CTTTTTT-CT

Variant names:

• chr8-30679706-CTTTTT-C
• rs10715710
• NM_000637.5:c.1420-42_1420-38delAAAAA

Variant summary

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

The NM_000637.5(GSR):​c.1420-42_1420-38delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,170,260 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSR NM_000637.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 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.1420-42_1420-38delAAAAA		intron	N/A	NP_000628.2	P00390-1
	GSR	NM_001195102.3		c.1333-42_1333-38delAAAAA		intron	N/A	NP_001182031.1	P00390-3
	GSR	NM_001195103.3		c.1261-42_1261-38delAAAAA		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.1420-42_1420-38delAAAAA		intron	N/A	ENSP00000221130.5	P00390-1
	GSR	ENST00000546342.5	TSL:1	c.1333-42_1333-38delAAAAA		intron	N/A	ENSP00000445516.1	P00390-3
	GSR	ENST00000541648.5	TSL:1	c.1261-42_1261-38delAAAAA		intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 134860 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 149 AN: 1170260 Hom.: 0 AF XY: 0.000128 AC XY: 75 AN XY: 587404

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

African (AFR) AF: 0.000111 AC: 3 AN: 27034

American (AMR) AF: 0.000207 AC: 7 AN: 33818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21954

East Asian (EAS) AF: 0.0000618 AC: 2 AN: 32348

South Asian (SAS) AF: 0.0000801 AC: 6 AN: 74860

European-Finnish (FIN) AF: 0.000183 AC: 7 AN: 38318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3536

European-Non Finnish (NFE) AF: 0.000130 AC: 116 AN: 889430

Other (OTH) AF: 0.000163 AC: 8 AN: 48962

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 134860 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64890

African (AFR) AF: 0.00 AC: 0 AN: 37032

American (AMR) AF: 0.00 AC: 0 AN: 13154

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4590

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7334

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62386

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs10715710; hg19: chr8-30537223;