17-5384698-G-A

Variant names:

• chr17-5384698-G-A
• rs1058381
• NM_004703.6:c.*1475G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004703.6(RABEP1):​c.*1475G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 212,076 control chromosomes in the GnomAD database, including 21,902 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 0.44 (15149 hom., cov: 32)
  • Exomes 𝑓: 0.44 (6753 hom.)
• Consequence: RABEP1 NM_004703.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760
• Publications: 16 publications found

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]

NUP88 Gene-Disease associations (from GenCC):

• fetal akinesia deformation sequence 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.*1475G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000537505.6	NP_004694.2
NUP88	NM_002532.6	c.*1508C>T		downstream_gene_variant		ENST00000573584.6	NP_002523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.*1475G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_004703.6	ENSP00000445408.2
NUP88	ENST00000573584.6	c.*1508C>T		downstream_gene_variant		1	NM_002532.6	ENSP00000458954.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66070 AN: 151844 Hom.: 15140 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.444 AC: 26669 AN: 60114 Hom.: 6753 Cov.: 0 AF XY: 0.446 AC XY: 12414 AN XY: 27836

African (AFR) AF: 0.395 AC: 1079 AN: 2732

American (AMR) AF: 0.374 AC: 674 AN: 1804

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1412 AN: 3902

East Asian (EAS) AF: 0.835 AC: 7124 AN: 8528

South Asian (SAS) AF: 0.624 AC: 327 AN: 524

European-Finnish (FIN) AF: 0.476 AC: 20 AN: 42

Middle Eastern (MID) AF: 0.500 AC: 191 AN: 382

European-Non Finnish (NFE) AF: 0.371 AC: 13807 AN: 37216

Other (OTH) AF: 0.408 AC: 2035 AN: 4984

GnomAD4 genome AF: 0.435 AC: 66123 AN: 151962 Hom.: 15149 Cov.: 32 AF XY: 0.451 AC XY: 33467 AN XY: 74268

African (AFR) AF: 0.414 AC: 17137 AN: 41416

American (AMR) AF: 0.413 AC: 6299 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3468

East Asian (EAS) AF: 0.837 AC: 4334 AN: 5176

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4816

European-Finnish (FIN) AF: 0.588 AC: 6200 AN: 10546

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26479 AN: 67954

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.390 Hom.: 17773

Bravo AF: 0.419

Asia WGS AF: 0.746 AC: 2589 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.76
Mutation Taster		=100/0	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: rs1058381; hg19: chr17-5288018;