NM_024816.3:c.1609-10G>A

Variant names:

• chr16-28905054-C-T
• rs4072997
• NM_024816.3:c.1609-10G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024816.3(RABEP2):​c.1609-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,596,044 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (12 hom.)
• Consequence: RABEP2 NM_024816.3 intron
• Scores: Splicing: ADA: 0.00008577
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15
• Publications: 0 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-28905054-C-T is Benign according to our data. Variant chr16-28905054-C-T is described in ClinVar as [Benign]. Clinvar id is 710473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1609-10G>A		intron_variant	Intron 12 of 12	ENST00000358201.9	NP_079092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9	c.1609-10G>A		intron_variant	Intron 12 of 12	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1501-10G>A		intron_variant	Intron 10 of 10	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1396-10G>A		intron_variant	Intron 11 of 11	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152112 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00269 AC: 631 AN: 234454 AF XY: 0.00294

Gnomad AFR exome AF: 0.000539

Gnomad AMR exome AF: 0.000882

Gnomad ASJ exome AF: 0.00791

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00440

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00324

GnomAD4 exome AF: 0.00327 AC: 4716 AN: 1443814 Hom.: 12 Cov.: 30 AF XY: 0.00326 AC XY: 2342 AN XY: 717732

African (AFR) AF: 0.000510 AC: 17 AN: 33340

American (AMR) AF: 0.00101 AC: 45 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 172 AN: 25912

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39500

South Asian (SAS) AF: 0.00258 AC: 221 AN: 85784

European-Finnish (FIN) AF: 0.00370 AC: 159 AN: 42960

Middle Eastern (MID) AF: 0.00813 AC: 45 AN: 5538

European-Non Finnish (NFE) AF: 0.00345 AC: 3815 AN: 1106530

Other (OTH) AF: 0.00401 AC: 240 AN: 59860

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.00214 AC XY: 159 AN XY: 74426

African (AFR) AF: 0.000650 AC: 27 AN: 41546

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4826

European-Finnish (FIN) AF: 0.00528 AC: 56 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 67994

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.012
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: rs4072997; hg19: chr16-28916375;