NM_002884.4:c.184-899G>A

Variant names:

• chr1-111702437-G-A
• rs4838920
• NM_002884.4:c.184-899G>A

Variant summary

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

The NM_002884.4(RAP1A):​c.184-899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,096 control chromosomes in the GnomAD database, including 1,615 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 (1615 hom., cov: 32)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 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.184-899G>A		intron	N/A	NP_002875.1
	RAP1A	NM_001010935.3		c.184-899G>A		intron	N/A	NP_001010935.1
	RAP1A	NM_001291896.3		c.184-899G>A		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.184-899G>A		intron	N/A	ENSP00000358723.3
	RAP1A	ENST00000356415.5	TSL:1	c.184-899G>A		intron	N/A	ENSP00000348786.1
	RAP1A	ENST00000687939.1		c.184-899G>A		intron	N/A	ENSP00000509234.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19667 AN: 151978 Hom.: 1609 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.129 AC: 19683 AN: 152096 Hom.: 1615 Cov.: 32 AF XY: 0.131 AC XY: 9716 AN XY: 74334

African (AFR) AF: 0.0364 AC: 1513 AN: 41518

American (AMR) AF: 0.133 AC: 2035 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3468

East Asian (EAS) AF: 0.146 AC: 753 AN: 5172

South Asian (SAS) AF: 0.177 AC: 852 AN: 4826

European-Finnish (FIN) AF: 0.221 AC: 2329 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11089 AN: 67992

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.139 Hom.: 270

Bravo AF: 0.119

Asia WGS AF: 0.193 AC: 668 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.59
PhyloP100		0.61
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: rs4838920; hg19: chr1-112245059;