chr17-7312491-T-C

Variant names:

• chr17-7312491-T-C
• rs8075575
• ENST00000570780.5:c.969+538A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 3 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]

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

ENSG00000261915 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	NM_004489.5	MANE Select	c.*265A>G		downstream_gene	N/A	NP_004480.1
	EIF5A	NM_001970.5	MANE Select	c.*681T>C		downstream_gene	N/A	NP_001961.1
	EIF5A	NM_001143760.1		c.*681T>C		downstream_gene	N/A	NP_001137232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	ENST00000570780.5	TSL:5	c.969+538A>G		intron	N/A	ENSP00000460836.1
	GPS2	ENST00000380728.7	TSL:1 MANE Select	c.*265A>G		downstream_gene	N/A	ENSP00000370104.2
	EIF5A	ENST00000336458.13	TSL:1 MANE Select	c.*681T>C		downstream_gene	N/A	ENSP00000336776.8

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5188 AN: 152010 Hom.: 279 Cov.: 32

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.: 69 Cov.: 0 AF XY: 0.00376 AC XY: 557 AN XY: 148174

African (AFR) AF: 0.110 AC: 920 AN: 8330

American (AMR) AF: 0.00621 AC: 68 AN: 10942

Ashkenazi Jewish (ASJ) AF: 0.00632 AC: 56 AN: 8862

East Asian (EAS) AF: 0.00 AC: 0 AN: 17934

South Asian (SAS) AF: 0.000259 AC: 8 AN: 30908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20110

Middle Eastern (MID) AF: 0.00835 AC: 10 AN: 1198

European-Non Finnish (NFE) AF: 0.000322 AC: 54 AN: 167506

Other (OTH) AF: 0.00940 AC: 155 AN: 16494

GnomAD4 genome AF: 0.0343 AC: 5213 AN: 152128 Hom.: 283 Cov.: 32 AF XY: 0.0330 AC XY: 2456 AN XY: 74374

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: 24 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 68000

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.0272 Hom.: 34

Bravo AF: 0.0380

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.63
DANN	Benign	0.77
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8075575; hg19: chr17-7215810;