Genetic Variant GSR:c.423-287G>A (chr8-30708428-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000637.5(GSR):c.423-287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,134 control chromosomes in the GnomAD database, including 23,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 23743 hom., cov: 33)

Consequence

GSR
NM_000637.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.69

Publications

24 publications found

Variant links:

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

GSR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 8-30708428-C-T is Benign according to our data. Variant chr8-30708428-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258539.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSR	NM_000637.5 link	c.423-287G>A		intron_variant	Intron 3 of 12	ENST00000221130.11	NP_000628.2	P00390-1V9HW90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSR	ENST00000221130.11 link	c.423-287G>A		intron_variant	Intron 3 of 12	1	NM_000637.5	ENSP00000221130.5		P00390-1

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81251

AN:

152016

Hom.:

23732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.671

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.533

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

GnomAD4 genome

AF:

0.534

AC:

81286

AN:

152134

Hom.:

23743

Cov.:

AF XY:

0.542

AC XY:

40321

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.278

AC:

11557

AN:

41508

American (AMR)

AF:

0.625

AC:

9549

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2011

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2479

AN:

5168

South Asian (SAS)

AF:

0.671

AC:

3240

AN:

4826

European-Finnish (FIN)

AF:

0.742

AC:

7842

AN:

10572

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42874

AN:

67998

Other (OTH)

AF:

0.533

AC:

1123

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1829

3657

5486

7314

9143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.600

Hom.:

120888

Bravo

AF:

0.513

Asia WGS

AF:

0.558

AC:

1940

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.46

(source)

DANN

Benign

0.31

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over