chr17-3007190-G-A

Variant names:

• chr17-3007190-G-A
• rs894664
• NM_015085.5:c.1360-821G>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.1360-821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,096 control chromosomes in the GnomAD database, including 1,947 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 0.15 (1947 hom., cov: 31)
• Consequence: RAP1GAP2 NM_015085.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	NM_015085.5	MANE Select	c.1360-821G>A		intron	N/A	NP_055900.4
	RAP1GAP2	NM_001411048.1		c.1483-821G>A		intron	N/A	NP_001397977.1
	RAP1GAP2	NM_001438816.1		c.1438-821G>A		intron	N/A	NP_001425745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GAP2	ENST00000254695.13	TSL:1 MANE Select	c.1360-821G>A		intron	N/A	ENSP00000254695.8
	RAP1GAP2	ENST00000366401.8	TSL:1	c.1315-821G>A		intron	N/A	ENSP00000389824.2
	RAP1GAP2	ENST00000637138.1	TSL:5	c.1483-821G>A		intron	N/A	ENSP00000490321.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22518 AN: 151978 Hom.: 1947 Cov.: 31

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.148 AC: 22521 AN: 152096 Hom.: 1947 Cov.: 31 AF XY: 0.147 AC XY: 10930 AN XY: 74336

African (AFR) AF: 0.0632 AC: 2621 AN: 41494

American (AMR) AF: 0.170 AC: 2595 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 947 AN: 3462

East Asian (EAS) AF: 0.156 AC: 802 AN: 5154

South Asian (SAS) AF: 0.127 AC: 611 AN: 4820

European-Finnish (FIN) AF: 0.130 AC: 1380 AN: 10586

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12972 AN: 67970

Other (OTH) AF: 0.186 AC: 393 AN: 2116

Alfa AF: 0.147 Hom.: 601

Bravo AF: 0.148

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		0.46
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: rs894664; hg19: chr17-2910484;