NM_004703.6:c.*2217A>G

Variant names:

• chr17-5385440-A-G
• rs1058398
• NM_004703.6:c.*2217A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 20 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=-0.3).
• 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 rank	MANE	Protein	UniProt
RABEP1	NM_004703.6	c.*2217A>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000537505.6	NP_004694.2
NUP88	NM_002532.6	c.*766T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000573584.6	NP_002523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6	c.*2217A>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_004703.6	ENSP00000445408.2
NUP88	ENST00000573584.6	c.*766T>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_002532.6	ENSP00000458954.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68037 AN: 151618 Hom.: 15642 Cov.: 32

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.: 0 AF XY: 0.433 AC XY: 15594 AN XY: 36002

African (AFR) AF: 0.494 AC: 1853 AN: 3750

American (AMR) AF: 0.406 AC: 971 AN: 2394

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1838 AN: 4956

East Asian (EAS) AF: 0.667 AC: 7297 AN: 10944

South Asian (SAS) AF: 0.553 AC: 366 AN: 662

European-Finnish (FIN) AF: 0.482 AC: 27 AN: 56

Middle Eastern (MID) AF: 0.494 AC: 233 AN: 472

European-Non Finnish (NFE) AF: 0.383 AC: 18498 AN: 48318

Other (OTH) AF: 0.418 AC: 2742 AN: 6556

GnomAD4 genome AF: 0.449 AC: 68091 AN: 151736 Hom.: 15649 Cov.: 32 AF XY: 0.460 AC XY: 34099 AN XY: 74162

African (AFR) AF: 0.496 AC: 20516 AN: 41386

American (AMR) AF: 0.419 AC: 6403 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3409 AN: 5132

South Asian (SAS) AF: 0.554 AC: 2667 AN: 4818

European-Finnish (FIN) AF: 0.585 AC: 6145 AN: 10504

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.389 AC: 26388 AN: 67862

Other (OTH) AF: 0.427 AC: 898 AN: 2102

Alfa AF: 0.409 Hom.: 36489

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	14
DANN	Benign	0.88
PhyloP100		1.6
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: rs1058398; hg19: chr17-5288760; COSMIC: COSV52585339; COSMIC: COSV52585339;