dbSNP rs8075575: GPS2:c.969+538A>G (chr17-7312491-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000570780.5(GPS2):c.969+538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 434,412 control chromosomes in the GnomAD database, including 352 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 0.034 ( 283 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 69 hom. )

Consequence

GPS2
ENST00000570780.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

Publications

3 publications found

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:

EIF5A (HGNC:3300): (eukaryotic translation initiation factor 5A) Enables U6 snRNA binding activity and protein N-terminus binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytoplasm; and nucleus. Part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

EIF5A Gene-Disease associations (from GenCC):

Faundes-Banka syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

EIF5A links:

ENSG00000261915 (HGNC:):

ENSG00000261915 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPS2	NM_004489.5 link	c.*265A>G		downstream_gene_variant		ENST00000380728.7	NP_004480.1	Q13227-1
EIF5A	NM_001970.5 link	c.*681T>C		downstream_gene_variant		ENST00000336458.13	NP_001961.1	P63241-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GPS2	ENST00000380728.7 link	c.*265A>G	downstream_gene_variant	1	NM_004489.5	ENSP00000370104.2	Q13227-1
EIF5A	ENST00000336458.13 link	c.*681T>C	downstream_gene_variant	1	NM_001970.5	ENSP00000336776.8	P63241-1
ENSG00000261915	ENST00000575474.1 link	n.*1524A>G	downstream_gene_variant	5		ENSP00000468772.1	K7ESM1

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5188

AN:

152010

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.00450

AC:

1271

AN:

282284

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

557

AN XY:

148174

show subpopulations

African (AFR)

AF:

0.110

AC:

920

AN:

8330

American (AMR)

AF:

0.00621

AC:

AN:

10942

Ashkenazi Jewish (ASJ)

AF:

0.00632

AC:

AN:

8862

East Asian (EAS)

AF:

0.00

AC:

AN:

17934

South Asian (SAS)

AF:

0.000259

AC:

AN:

30908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20110

Middle Eastern (MID)

AF:

0.00835

AC:

AN:

1198

European-Non Finnish (NFE)

AF:

0.000322

AC:

AN:

167506

Other (OTH)

AF:

0.00940

AC:

155

AN:

16494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0343

AC:

5213

AN:

152128

Hom.:

283

Cov.:

AF XY:

0.0330

AC XY:

2456

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.117

AC:

4868

AN:

41462

American (AMR)

AF:

0.0149

AC:

228

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

68000

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

233

465

698

930

1163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0272

Hom.:

Bravo

AF:

0.0380

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.63

(source)

DANN

Benign

0.77

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over