16-28905724-C-T

Variant names:

• chr16-28905724-C-T
• rs201409528
• NM_024816.3:c.1471G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024816.3(RABEP2):​c.1471G>A​(p.Val491Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V491L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• Publications: 2 publications found

Genes affected

RABEP2 (HGNC:24817): (rabaptin, RAB GTPase binding effector protein 2) Predicted to enable GTPase activator activity and growth factor activity. Involved in regulation of cilium assembly. Located in cytosol; intracellular membrane-bounded organelle; and microtubule organizing center. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074278414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1471G>A	p.Val491Met	missense_variant	Exon 11 of 13	ENST00000358201.9	NP_079092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9	c.1471G>A	p.Val491Met	missense_variant	Exon 11 of 13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1363G>A	p.Val455Met	missense_variant	Exon 9 of 11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1258G>A	p.Val420Met	missense_variant	Exon 10 of 12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000306 AC: 76 AN: 248722 AF XY: 0.000244

Gnomad AFR exome AF: 0.00428

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000999 AC: 146 AN: 1461690 Hom.: 0 Cov.: 34 AF XY: 0.0000798 AC XY: 58 AN XY: 727136

African (AFR) AF: 0.00385 AC: 129 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111922

Other (OTH) AF: 0.0000828 AC: 5 AN: 60384

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74494

African (AFR) AF: 0.00428 AC: 178 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00000973 Hom.: 0

Bravo AF: 0.00116

ESP6500AA AF: 0.00441 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000364 AC: 44

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0074	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.2	.;L;.
PhyloP100		-0.55
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.92	N;N;N
REVEL	Benign	0.086
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.88	P;B;P
Vest4		0.28
MVP		0.34
MPC		0.18
ClinPred		0.074	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.071
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201409528; hg19: chr16-28917045;