chr17-7313221-G-A

Variant names:

• chr17-7313221-G-A
• rs2270981
• NM_004489.5:c.795C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004489.5(GPS2):​c.795C>T​(p.Phe265Phe) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 17 publications found

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]

ENSG00000261915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPS2	NM_004489.5	c.795C>T	p.Phe265Phe	synonymous_variant	Exon 9 of 11	ENST00000380728.7	NP_004480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPS2	ENST00000380728.7	c.795C>T	p.Phe265Phe	synonymous_variant	Exon 9 of 11	1	NM_004489.5	ENSP00000370104.2
ENSG00000261915	ENST00000575474.1	n.*1070C>T		non_coding_transcript_exon_variant	Exon 17 of 19	5		ENSP00000468772.1
ENSG00000261915	ENST00000575474.1	n.*1070C>T		3_prime_UTR_variant	Exon 17 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8444 AN: 152180 Hom.: 411 Cov.: 32

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

GnomAD2 exomes AF: 0.0707 AC: 17761 AN: 251182 AF XY: 0.0686

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 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.: 31 AF XY: 0.0563 AC XY: 40926 AN XY: 727124

African (AFR) AF: 0.0331 AC: 1109 AN: 33472

American (AMR) AF: 0.0829 AC: 3707 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2805 AN: 26132

East Asian (EAS) AF: 0.263 AC: 10453 AN: 39698

South Asian (SAS) AF: 0.0652 AC: 5622 AN: 86248

European-Finnish (FIN) AF: 0.0327 AC: 1746 AN: 53392

Middle Eastern (MID) AF: 0.0420 AC: 242 AN: 5766

European-Non Finnish (NFE) AF: 0.0472 AC: 52422 AN: 1111802

Other (OTH) AF: 0.0738 AC: 4456 AN: 60380

GnomAD4 genome AF: 0.0554 AC: 8441 AN: 152298 Hom.: 412 Cov.: 32 AF XY: 0.0571 AC XY: 4255 AN XY: 74472

African (AFR) AF: 0.0367 AC: 1527 AN: 41560

American (AMR) AF: 0.0785 AC: 1201 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1410 AN: 5172

South Asian (SAS) AF: 0.0683 AC: 330 AN: 4832

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10616

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3047 AN: 68028

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0526 Hom.: 1472

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	13
DANN	Benign	0.83
PhyloP100		2.4
PromoterAI		-0.024	Neutral
Mutation Taster		=81/19	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270981; hg19: chr17-7216540; COSMIC: COSV59747073; COSMIC: COSV59747073;