NM_002884.4:c.*29+1511G>A

Variant names:

• chr1-111710775-G-A
• rs846261
• NM_002884.4:c.*29+1511G>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.*29+1511G>A 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 152,252 control chromosomes in the GnomAD database, including 1,539 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 (1539 hom., cov: 33)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.*29+1511G>A		intron_variant	Intron 7 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.*29+1511G>A		intron_variant	Intron 7 of 7	1	NM_002884.4	ENSP00000358723.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20052 AN: 152132 Hom.: 1541 Cov.: 33

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.132 AC: 20055 AN: 152252 Hom.: 1539 Cov.: 33 AF XY: 0.134 AC XY: 9995 AN XY: 74444

African (AFR) AF: 0.0805 AC: 3343 AN: 41550

American (AMR) AF: 0.189 AC: 2887 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1088 AN: 5184

South Asian (SAS) AF: 0.113 AC: 544 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1883 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9367 AN: 68010

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.135 Hom.: 1032

Bravo AF: 0.132

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		3.2
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: rs846261; hg19: chr1-112253397;