rs1065483

chr17-5381475-G-Achr17-5381475-G-Cchr17-5381475-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004703.6(RABEP1):c.2457G>A(p.Arg819=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,610,816 control chromosomes in the GnomAD database, including 187,492 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 (21594 hom., cov: 32)
  • Exomes 𝑓: 0.46 (165898 hom.)
• Consequence: RABEP1 NM_004703.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461

Genes affected

RABEP1 (HGNC:17677): (rabaptin, RAB GTPase binding effector protein 1) Enables protein domain specific binding activity and protein homodimerization activity. Involved in vesicle-mediated transport. Located in endocytic vesicle and endosome. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

NUP88 (HGNC:8067): (nucleoporin 88) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.461 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABEP1	NM_004703.6	c.2457G>A	p.Arg819=	synonymous_variant	17/18	ENST00000537505.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP1	ENST00000537505.6	c.2457G>A	p.Arg819=	synonymous_variant	17/18	1	NM_004703.6	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78234 AN: 151900 Hom.: 21554 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.493

GnomAD3 exomes AF: 0.533 AC: 132450 AN: 248518 Hom.: 38952 AF XY: 0.535 AC XY: 72103 AN XY: 134804

Gnomad AFR exome AF: 0.612

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.972

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.493

GnomAD4 exome AF: 0.460 AC: 670737 AN: 1458798 Hom.: 165898 Cov.: 41 AF XY: 0.467 AC XY: 338614 AN XY: 725640

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.722

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.515 AC: 78337 AN: 152018 Hom.: 21594 Cov.: 32 AF XY: 0.531 AC XY: 39429 AN XY: 74312

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.498

Alfa AF: 0.433 Hom.: 24402

Bravo AF: 0.508

Asia WGS AF: 0.835 AC: 2898 AN: 3478

EpiCase AF: 0.410

EpiControl AF: 0.410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	5.5
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs1065483; hg19: chr17-5284770; COSMIC: COSV52583947; COSMIC: COSV52583947;