rs1076165

Variant names:

• chr17-2870106-G-A
• rs1076165
• NM_015085.5:c.81-35178G>A

Variant summary

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

The NM_015085.5(RAP1GAP2):​c.81-35178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,482 control chromosomes in the GnomAD database, including 1,716 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 0.10 (1716 hom., cov: 31)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• Publications: 2 publications found

Genes affected

RAP1GAP2 (HGNC:29176): (RAP1 GTPase activating protein 2) This gene encodes a GTPase-activating protein that activates the small guanine-nucleotide-binding protein Rap1 in platelets. The protein interacts with synaptotagmin-like protein 1 and Rab27 and regulates secretion of dense granules from platelets at sites of endothelial damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GAP2	NM_015085.5	c.81-35178G>A		intron_variant	Intron 2 of 24	ENST00000254695.13	NP_055900.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GAP2	ENST00000254695.13	c.81-35178G>A		intron_variant	Intron 2 of 24	1	NM_015085.5	ENSP00000254695.8

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15267 AN: 151366 Hom.: 1706 Cov.: 31

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0978

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15292 AN: 151482 Hom.: 1716 Cov.: 31 AF XY: 0.111 AC XY: 8213 AN XY: 73974

African (AFR) AF: 0.0408 AC: 1684 AN: 41322

American (AMR) AF: 0.196 AC: 2968 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3466

East Asian (EAS) AF: 0.586 AC: 2966 AN: 5064

South Asian (SAS) AF: 0.176 AC: 843 AN: 4788

European-Finnish (FIN) AF: 0.188 AC: 1971 AN: 10476

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0645 AC: 4377 AN: 67880

Other (OTH) AF: 0.103 AC: 217 AN: 2108

Alfa AF: 0.0828 Hom.: 111

Bravo AF: 0.106

Asia WGS AF: 0.356 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1076165; hg19: chr17-2773400;