rs10776733

Positions:

• chr1-111565047-A-G
• chr1-111565047-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370216.2(RAP1A):​c.-28+22538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,936 control chromosomes in the GnomAD database, including 25,945 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 0.58 (25945 hom., cov: 31)
• Consequence: RAP1A NM_001370216.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_001370216.2	c.-28+22538A>G		intron_variant			NP_001357145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000356415.5	c.-28+22538A>G		intron_variant		1		ENSP00000348786.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88351 AN: 151816 Hom.: 25952 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.582 AC: 88358 AN: 151936 Hom.: 25945 Cov.: 31 AF XY: 0.585 AC XY: 43461 AN XY: 74238

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.579

Alfa AF: 0.594 Hom.: 36419

Bravo AF: 0.577

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs10776733; hg19: chr1-112107669;