Variant 17-7313221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004489.5(GPS2):c.795C>T(p.Phe265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 1,613,912 control chromosomes in the GnomAD database, including 3,985 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 0.055 ( 412 hom., cov: 32)

Exomes 𝑓: 0.056 ( 3573 hom. )

Consequence

GPS2
NM_004489.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.44

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=-0.5).

BP7

Synonymous conserved (PhyloP=2.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 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.795C>T	p.Phe265=	synonymous_variant	9/11	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.795C>T	p.Phe265=	synonymous_variant	9/11	1	NM_004489.5	ENSP00000370104	P1	Q13227-1

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8444

AN:

152180

Hom.:

411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0650

GnomAD3 exomes

AF:

0.0707

AC:

17761

AN:

251182

Hom.:

1126

AF XY:

0.0686

AC XY:

9317

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.0835

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.0677

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0433

Gnomad OTH exome

AF:

0.0666

GnomAD4 exome

AF:

0.0565

AC:

82562

AN:

1461614

Hom.:

3573

Cov.:

AF XY:

0.0563

AC XY:

40926

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0331

Gnomad4 AMR exome

AF:

0.0829

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.263

Gnomad4 SAS exome

AF:

0.0652

Gnomad4 FIN exome

AF:

0.0327

Gnomad4 NFE exome

AF:

0.0472

Gnomad4 OTH exome

AF:

0.0738

GnomAD4 genome

AF:

0.0554

AC:

8441

AN:

152298

Hom.:

412

Cov.:

AF XY:

0.0571

AC XY:

4255

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0367

Gnomad4 AMR

AF:

0.0785

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.0683

Gnomad4 FIN

AF:

0.0363

Gnomad4 NFE

AF:

0.0448

Gnomad4 OTH

AF:

0.0681

Alfa

AF:

0.0507

Hom.:

640

Bravo

AF:

0.0612

Asia WGS

AF:

0.180

AC:

626

AN:

3478

EpiCase

AF:

0.0427

EpiControl

AF:

0.0433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.83

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