rs1800668

Variant names:

Variant summary

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

The NM_000581.4(GPX1):c.-46C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,500,264 control chromosomes in the GnomAD database, including 70,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6569 hom., cov: 33)

Exomes 𝑓: 0.30 ( 64249 hom. )

Consequence

GPX1
NM_000581.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.81

Publications

98 publications found

Variant links:

Genes affected

GPX1 (HGNC:4553): (glutathione peroxidase 1) The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Other studies indicate that H2O2 is also essential for growth-factor mediated signal transduction, mitochondrial function, and maintenance of thiol redox-balance; therefore, by limiting H2O2 accumulation, glutathione peroxidases are also involved in modulating these processes. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is the most abundant, is ubiquitously expressed and localized in the cytoplasm, and whose preferred substrate is hydrogen peroxide. It is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. This gene contains an in-frame GCG trinucleotide repeat in the coding region, and three alleles with 4, 5 or 6 repeats have been found in the human population. The allele with 4 GCG repeats has been significantly associated with breast cancer risk in premenopausal women. Alternatively spliced transcript variants have been found for this gene. Pseudogenes of this locus have been identified on chromosomes X and 21. [provided by RefSeq, Aug 2017]

GPX1 links:

ENSG00000290318 (HGNC:):

ENSG00000290318 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=-0.7).

BP6

Variant 3-49358324-G-A is Benign according to our data. Variant chr3-49358324-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPX1	NM_000581.4	MANE Select	c.-46C>T	5_prime_UTR	Exon 1 of 2	NP_000572.2
GPX1	NM_001329503.2		c.-46C>T	5_prime_UTR	Exon 1 of 2	NP_001316432.1
GPX1	NM_001329455.2		c.-46C>T	5_prime_UTR	Exon 1 of 2	NP_001316384.1	A0A2R8Y6B6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GPX1	ENST00000419783.3	TSL:1 MANE Select	c.-46C>T	5_prime_UTR	Exon 1 of 2	ENSP00000407375.1	P07203-1
ENSG00000290318	ENST00000704381.1		c.465-577C>T	intron	N/A	ENSP00000515884.1	A0A994J514
GPX1	ENST00000703795.1		c.-46C>T	5_prime_UTR	Exon 1 of 2	ENSP00000515480.1	A0A994J430

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42711

AN:

152034

Hom.:

6567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.295

AC:

33864

AN:

114888

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.0572

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.302

AC:

407576

AN:

1348112

Hom.:

64249

Cov.:

AF XY:

0.301

AC XY:

198941

AN XY:

660102

show subpopulations

African (AFR)

AF:

0.240

AC:

7168

AN:

29818

American (AMR)

AF:

0.191

AC:

5339

AN:

27948

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

10291

AN:

22270

East Asian (EAS)

AF:

0.0631

AC:

2213

AN:

35046

South Asian (SAS)

AF:

0.248

AC:

18138

AN:

73066

European-Finnish (FIN)

AF:

0.457

AC:

21172

AN:

46302

Middle Eastern (MID)

AF:

0.334

AC:

1280

AN:

3838

European-Non Finnish (NFE)

AF:

0.308

AC:

325220

AN:

1054336

Other (OTH)

AF:

0.302

AC:

16755

AN:

55488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

15760

31520

47280

63040

78800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10832

21664

32496

43328

54160

<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:

0.281

AC:

42726

AN:

152152

Hom.:

6569

Cov.:

AF XY:

0.284

AC XY:

21107

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.235

AC:

9738

AN:

41514

American (AMR)

AF:

0.216

AC:

3294

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1601

AN:

3472

East Asian (EAS)

AF:

0.0586

AC:

303

AN:

5174

South Asian (SAS)

AF:

0.226

AC:

1092

AN:

4822

European-Finnish (FIN)

AF:

0.472

AC:

4998

AN:

10598

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20825

AN:

67984

Other (OTH)

AF:

0.285

AC:

601

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1548

3095

4643

6190

7738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.284

Hom.:

2681

Bravo

AF:

0.258

Asia WGS

AF:

0.143

AC:

502

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

-0.70

CADD

Benign

4.6

(source)

DANN

Benign

0.67

PhyloP100

-1.8

PromoterAI

0.21

Neutral

(source)

Mutation Taster

=300/0

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