dbSNP rs2250192: GSR:c.1154-45A>C (chr8-30682106-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000637.5(GSR):c.1154-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,559,624 control chromosomes in the GnomAD database, including 466,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42298 hom., cov: 33)

Exomes 𝑓: 0.78 ( 424011 hom. )

Consequence

GSR
NM_000637.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.384

Publications

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

GSR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-30682106-T-G is Benign according to our data. Variant chr8-30682106-T-G is described in ClinVar as Benign. ClinVar VariationId is 1272685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSR	NM_000637.5	MANE Select	c.1154-45A>C	intron	N/A	NP_000628.2	P00390-1
GSR	NM_001195102.3		c.1067-45A>C	intron	N/A	NP_001182031.1	P00390-3
GSR	NM_001195103.3		c.995-45A>C	intron	N/A	NP_001182032.1	P00390-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSR	ENST00000221130.11	TSL:1 MANE Select	c.1154-45A>C	intron	N/A	ENSP00000221130.5	P00390-1
GSR	ENST00000546342.5	TSL:1	c.1067-45A>C	intron	N/A	ENSP00000445516.1	P00390-3
GSR	ENST00000541648.5	TSL:1	c.995-45A>C	intron	N/A	ENSP00000444559.1	P00390-4

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112785

AN:

151930

Hom.:

42283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.638

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.717

Gnomad FIN

AF:

0.781

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.790

GnomAD2 exomes

AF:

0.779

AC:

194531

AN:

249684

AF XY:

0.779

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.805

Gnomad ASJ exome

AF:

0.833

Gnomad EAS exome

AF:

0.902

Gnomad FIN exome

AF:

0.773

Gnomad NFE exome

AF:

0.780

Gnomad OTH exome

AF:

0.788

GnomAD4 exome

AF:

0.775

AC:

1091384

AN:

1407576

Hom.:

424011

Cov.:

AF XY:

0.774

AC XY:

544387

AN XY:

703504

show subpopulations

African (AFR)

AF:

0.623

AC:

20155

AN:

32326

American (AMR)

AF:

0.804

AC:

35889

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

21624

AN:

25732

East Asian (EAS)

AF:

0.878

AC:

34554

AN:

39364

South Asian (SAS)

AF:

0.729

AC:

62002

AN:

85078

European-Finnish (FIN)

AF:

0.771

AC:

40764

AN:

52840

Middle Eastern (MID)

AF:

0.778

AC:

4373

AN:

5620

European-Non Finnish (NFE)

AF:

0.777

AC:

826325

AN:

1063354

Other (OTH)

AF:

0.780

AC:

45698

AN:

58606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

12656

25313

37969

50626

63282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19358

38716

58074

77432

96790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.742

AC:

112850

AN:

152048

Hom.:

42298

Cov.:

AF XY:

0.744

AC XY:

55269

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.638

AC:

26461

AN:

41460

American (AMR)

AF:

0.786

AC:

11981

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

2898

AN:

3472

East Asian (EAS)

AF:

0.902

AC:

4667

AN:

5176

South Asian (SAS)

AF:

0.718

AC:

3463

AN:

4824

European-Finnish (FIN)

AF:

0.781

AC:

8248

AN:

10556

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.774

AC:

52602

AN:

67996

Other (OTH)

AF:

0.787

AC:

1661

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1486

2972

4457

5943

7429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.760

Hom.:

24150

Bravo

AF:

0.743

Asia WGS

AF:

0.801

AC:

2784

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

0.38

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over