Variant chr17-7314144-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000380728.7(GPS2):c.333A>G(p.Leu111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,612,252 control chromosomes in the GnomAD database, including 238,538 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 0.52 ( 21240 hom., cov: 31)

Exomes 𝑓: 0.54 ( 217298 hom. )

Consequence

GPS2
ENST00000380728.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

GPS2 (HGNC:4550): (G protein pathway suppressor 2) This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

GPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP7

Synonymous conserved (PhyloP=1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPS2	NM_004489.5 linkuse as main transcript	c.333A>G	p.Leu111=	synonymous_variant	5/11	ENST00000380728.7	NP_004480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPS2	ENST00000380728.7 linkuse as main transcript	c.333A>G	p.Leu111=	synonymous_variant	5/11	1	NM_004489.5	ENSP00000370104	P1	Q13227-1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79635

AN:

151784

Hom.:

21200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.563

AC:

141453

AN:

251466

Hom.:

40797

AF XY:

0.558

AC XY:

75808

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.469

Gnomad AMR exome

AF:

0.693

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.658

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.604

Gnomad NFE exome

AF:

0.517

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.542

AC:

791883

AN:

1460350

Hom.:

217298

Cov.:

AF XY:

0.542

AC XY:

393877

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.679

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.536

GnomAD4 genome

AF:

0.525

AC:

79730

AN:

151902

Hom.:

21240

Cov.:

AF XY:

0.530

AC XY:

39324

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.468

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.671

Gnomad4 SAS

AF:

0.607

Gnomad4 FIN

AF:

0.599

Gnomad4 NFE

AF:

0.522

Gnomad4 OTH

AF:

0.514

Alfa

AF:

0.510

Hom.:

20472

Bravo

AF:

0.522

Asia WGS

AF:

0.618

AC:

2147

AN:

3478

EpiCase

AF:

0.498

EpiControl

AF:

0.488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over