rs201409528

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-28905724-C-A
• chr16-28905724-C-T

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>T​(p.Val491Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.01383391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1471G>T	p.Val491Leu	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>T	p.Val491Leu	missense_variant	Exon 11 of 13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1363G>T	p.Val455Leu	missense_variant	Exon 9 of 11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1258G>T	p.Val420Leu	missense_variant	Exon 10 of 12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000298 AC: 74 AN: 248722 AF XY: 0.000274

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.000598

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000252 AC: 369 AN: 1461690 Hom.: 0 Cov.: 34 AF XY: 0.000253 AC XY: 184 AN XY: 727136

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00112 AC: 50 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000727 AC: 19 AN: 26134

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

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

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000236 AC: 262 AN: 1111922

Other (OTH) AF: 0.000464 AC: 28 AN: 60384

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.000295 AC XY: 22 AN XY: 74494

African (AFR) AF: 0.000265 AC: 11 AN: 41578

American (AMR) AF: 0.00216 AC: 33 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: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000749 Hom.: 0

Bravo AF: 0.000657

ExAC AF: 0.000248 AC: 30

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1471G>T (p.V491L) alteration is located in exon 11 (coding exon 11) of the RABEP2 gene. This alteration results from a G to T substitution at nucleotide position 1471, causing the valine (V) at amino acid position 491 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.83
DEOGEN2	Benign	0.086	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	.;L;.
PhyloP100		-0.55
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.57	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.061	B;B;B
Vest4		0.26
MutPred		0.42		.;Gain of relative solvent accessibility (P = 0.1571);.;
MVP		0.28
MPC		0.17
ClinPred		0.0049	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.063
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;