Variant 17-5385440-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004703.6(RABEP1):c.*2217A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 229,844 control chromosomes in the GnomAD database, including 23,392 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 0.45 ( 15649 hom., cov: 32)

Exomes 𝑓: 0.43 ( 7743 hom. )

Consequence

RABEP1
NM_004703.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

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]

NUP88 links:

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]

RABEP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP88	NM_002532.6 linkuse as main transcript	c.*766T>C		3_prime_UTR_variant	17/17	ENST00000573584.6
RABEP1	NM_004703.6 linkuse as main transcript	c.*2217A>G		3_prime_UTR_variant	18/18	ENST00000537505.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP1	ENST00000537505.6 linkuse as main transcript	c.*2217A>G		3_prime_UTR_variant	18/18	1	NM_004703.6	P1	Q15276-1
NUP88	ENST00000573584.6 linkuse as main transcript	c.*766T>C		3_prime_UTR_variant	17/17	1	NM_002532.6	P1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68037

AN:

151618

Hom.:

15642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.429

GnomAD4 exome

AF:

0.433

AC:

33825

AN:

78108

Hom.:

7743

Cov.:

AF XY:

0.433

AC XY:

15594

AN XY:

36002

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.667

Gnomad4 SAS exome

AF:

0.553

Gnomad4 FIN exome

AF:

0.482

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.449

AC:

68091

AN:

151736

Hom.:

15649

Cov.:

AF XY:

0.460

AC XY:

34099

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.419

Gnomad4 ASJ

AF:

0.387

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.585

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.404

Hom.:

20059

Bravo

AF:

0.439

Asia WGS

AF:

0.601

AC:

2085

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.88

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