rs72634030

Variant names:

• chr17-5369285-C-A
• rs72634030
• NM_004703.6:c.1884+817C>A

Variant summary

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

The NM_004703.6(RABEP1):​c.1884+817C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,116 control chromosomes in the GnomAD database, including 1,970 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 0.099 (1970 hom., cov: 32)
• Consequence: RABEP1 NM_004703.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 25 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

ENSG00000263220 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004703.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP1	NM_004703.6	MANE Select	c.1884+817C>A		intron	N/A	NP_004694.2
	RABEP1	NM_001083585.3		c.1884+817C>A		intron	N/A	NP_001077054.1
	RABEP1	NM_001291581.2		c.1755+817C>A		intron	N/A	NP_001278510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP1	ENST00000537505.6	TSL:1 MANE Select	c.1884+817C>A		intron	N/A	ENSP00000445408.2
	RABEP1	ENST00000341923.10	TSL:1	c.1884+817C>A		intron	N/A	ENSP00000339569.6
	NUP88	ENST00000573169.1	TSL:1	n.72-7199G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15013 AN: 151998 Hom.: 1977 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0981

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0987 AC: 15007 AN: 152116 Hom.: 1970 Cov.: 32 AF XY: 0.111 AC XY: 8219 AN XY: 74336

African (AFR) AF: 0.0160 AC: 663 AN: 41546

American (AMR) AF: 0.172 AC: 2634 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 301 AN: 3466

East Asian (EAS) AF: 0.628 AC: 3235 AN: 5148

South Asian (SAS) AF: 0.358 AC: 1718 AN: 4796

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10570

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0680 AC: 4624 AN: 68000

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0893 Hom.: 2660

Bravo AF: 0.0952

Asia WGS AF: 0.453 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72634030; hg19: chr17-5272580;