rs17028287

Variant names:

• chr1-111702176-A-T
• rs17028287
• NM_002884.4:c.184-1160A>T

Variant summary

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

The NM_002884.4(RAP1A):​c.184-1160A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,216 control chromosomes in the GnomAD database, including 2,033 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 0.13 (2033 hom., cov: 32)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768
• Publications: 6 publications found

Genes affected

RAP1A (HGNC:9855): (RAP1A, member of RAS oncogene family) This gene encodes a member of the Ras family of small GTPases. The encoded protein undergoes a change in conformational state and activity, depending on whether it is bound to GTP or GDP. This protein is activated by several types of guanine nucleotide exchange factors (GEFs), and inactivated by two groups of GTPase-activating proteins (GAPs). The activation status of the encoded protein is therefore affected by the balance of intracellular levels of GEFs and GAPs. The encoded protein regulates signaling pathways that affect cell proliferation and adhesion, and may play a role in tumor malignancy. Pseudogenes of this gene have been defined on chromosomes 14 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002884.4. 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
	RAP1A	NM_002884.4	MANE Select	c.184-1160A>T		intron	N/A	NP_002875.1
	RAP1A	NM_001010935.3		c.184-1160A>T		intron	N/A	NP_001010935.1
	RAP1A	NM_001291896.3		c.184-1160A>T		intron	N/A	NP_001278825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	ENST00000369709.4	TSL:1 MANE Select	c.184-1160A>T		intron	N/A	ENSP00000358723.3
	RAP1A	ENST00000356415.5	TSL:1	c.184-1160A>T		intron	N/A	ENSP00000348786.1
	RAP1A	ENST00000687939.1		c.184-1160A>T		intron	N/A	ENSP00000509234.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20105 AN: 152098 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.132 AC: 20134 AN: 152216 Hom.: 2033 Cov.: 32 AF XY: 0.131 AC XY: 9783 AN XY: 74424

African (AFR) AF: 0.293 AC: 12145 AN: 41504

American (AMR) AF: 0.100 AC: 1536 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.0821 AC: 426 AN: 5190

South Asian (SAS) AF: 0.0857 AC: 414 AN: 4832

European-Finnish (FIN) AF: 0.0753 AC: 797 AN: 10590

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0623 AC: 4239 AN: 68028

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.103 Hom.: 162

Bravo AF: 0.141

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.58
PhyloP100		0.77
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: rs17028287; hg19: chr1-112244798;