Genetic Variant GLRX:c.208-1880G>C (chr5-95818506-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001118890.2(GLRX):c.208-1880G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,986 control chromosomes in the GnomAD database, including 10,053 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 10051 hom., cov: 31)

Exomes 𝑓: 0.26 ( 2 hom. )

Consequence

GLRX
NM_001118890.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

6 publications found

Variant links:

Genes affected

GLRX (HGNC:4330): (glutaredoxin) This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer's disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2011]

GLRX links:

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RHOBTB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001118890.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLRX	NM_001118890.2	MANE Select	c.208-1880G>C	intron	N/A	NP_001112362.1	P35754
GLRX	NM_001243658.2		c.208-1880G>C	intron	N/A	NP_001230587.1	P35754
GLRX	NM_001243659.2		c.208-1880G>C	intron	N/A	NP_001230588.1	P35754

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLRX	ENST00000237858.11	TSL:1 MANE Select	c.208-1880G>C	intron	N/A	ENSP00000237858.6	P35754
GLRX	ENST00000379979.8	TSL:1	c.208-1880G>C	intron	N/A	ENSP00000369314.4	P35754
GLRX	ENST00000512469.2	TSL:1	c.208-1880G>C	intron	N/A	ENSP00000424636.2	P35754

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51715

AN:

151810

Hom.:

10035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.309

GnomAD4 exome

AF:

0.259

AC:

AN:

Hom.:

Cov.:

AF XY:

0.281

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.188

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.286

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.341

AC:

51786

AN:

151928

Hom.:

10051

Cov.:

AF XY:

0.344

AC XY:

25532

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.493

AC:

20391

AN:

41386

American (AMR)

AF:

0.353

AC:

5396

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

904

AN:

3472

East Asian (EAS)

AF:

0.683

AC:

3531

AN:

5170

South Asian (SAS)

AF:

0.229

AC:

1101

AN:

4812

European-Finnish (FIN)

AF:

0.315

AC:

3328

AN:

10550

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16150

AN:

67942

Other (OTH)

AF:

0.309

AC:

652

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1599

3198

4797

6396

7995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.0966

Hom.:

121

Bravo

AF:

0.357

Asia WGS

AF:

0.423

AC:

1469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.0

(source)

DANN

Benign

0.30

PhyloP100

0.12

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