16-28914657-T-C

Variant names:

• chr16-28914657-T-C
• rs3924376
• NM_024816.3:c.543+15A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024816.3(RABEP2):​c.543+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,613,346 control chromosomes in the GnomAD database, including 395,782 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 0.76 (44771 hom., cov: 32)
  • Exomes 𝑓: 0.69 (351011 hom.)
• Consequence: RABEP2 NM_024816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024816.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP2	NM_024816.3	MANE Select	c.543+15A>G		intron	N/A	NP_079092.2	Q9H5N1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEP2	ENST00000358201.9	TSL:1 MANE Select	c.543+15A>G		intron	N/A	ENSP00000350934.4	Q9H5N1-1
	RABEP2	ENST00000357573.10	TSL:1	c.543+15A>G		intron	N/A	ENSP00000350186.6	Q9H5N1-2
	RABEP2	ENST00000562590.5	TSL:1	n.1064+15A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114817 AN: 151990 Hom.: 44722 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.765

GnomAD2 exomes AF: 0.708 AC: 176070 AN: 248806 AF XY: 0.715

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.900

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.699

GnomAD4 exome AF: 0.689 AC: 1006731 AN: 1461240 Hom.: 351011 Cov.: 44 AF XY: 0.693 AC XY: 503552 AN XY: 726952

African (AFR) AF: 0.953 AC: 31903 AN: 33464

American (AMR) AF: 0.539 AC: 24062 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 19995 AN: 26104

East Asian (EAS) AF: 0.874 AC: 34686 AN: 39696

South Asian (SAS) AF: 0.818 AC: 70558 AN: 86218

European-Finnish (FIN) AF: 0.638 AC: 34063 AN: 53350

Middle Eastern (MID) AF: 0.835 AC: 4815 AN: 5766

European-Non Finnish (NFE) AF: 0.669 AC: 743263 AN: 1111592

Other (OTH) AF: 0.719 AC: 43386 AN: 60382

GnomAD4 genome AF: 0.755 AC: 114914 AN: 152106 Hom.: 44771 Cov.: 32 AF XY: 0.755 AC XY: 56127 AN XY: 74338

African (AFR) AF: 0.938 AC: 38982 AN: 41544

American (AMR) AF: 0.637 AC: 9724 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3466

East Asian (EAS) AF: 0.885 AC: 4564 AN: 5158

South Asian (SAS) AF: 0.827 AC: 3995 AN: 4828

European-Finnish (FIN) AF: 0.642 AC: 6791 AN: 10580

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45619 AN: 67948

Other (OTH) AF: 0.763 AC: 1609 AN: 2108

Alfa AF: 0.634 Hom.: 3377

Bravo AF: 0.761

Asia WGS AF: 0.798 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.016
DANN	Benign	0.33
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3924376;

hg19: chr16-28925978;