Genetic Variant NM_004703.6:c.*1475G>A (chr17-5384698-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.760

Publications

16 publications found

Variant links:

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]

RABEP1 links:

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

NUP88 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.*1475G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000537505.6	NP_004694.2	Q15276-1
NUP88	NM_002532.6 link	c.*1508C>T		downstream_gene_variant		ENST00000573584.6	NP_002523.2	Q99567

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP1	ENST00000537505.6 link	c.*1475G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_004703.6	ENSP00000445408.2		Q15276-1
NUP88	ENST00000573584.6 link	c.*1508C>T		downstream_gene_variant		1	NM_002532.6	ENSP00000458954.1		Q99567

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66070

AN:

151844

Hom.:

15140

Cov.:

show subpopulations

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.:

AF XY:

0.446

AC XY:

12414

AN XY:

27836

show subpopulations

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:

AN:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

622

1244

1866

2488

3110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66123

AN:

151962

Hom.:

15149

Cov.:

AF XY:

0.451

AC XY:

33467

AN XY:

74268

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1810

3620

5430

7240

9050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.89

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over