1-111565047-A-G

Variant names:

• chr1-111565047-A-G
• rs10776733
• ENST00000356415.5:c.-28+22538A>G

Variant summary

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

The ENST00000356415.5(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 ENST00000356415.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAP1A	NM_001370216.2	c.-28+22538A>G		intron_variant	Intron 1 of 7		NP_001357145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000356415.5	c.-28+22538A>G		intron_variant	Intron 1 of 7	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

African (AFR) AF: 0.523 AC: 21659 AN: 41416

American (AMR) AF: 0.598 AC: 9139 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2277 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3753 AN: 5158

South Asian (SAS) AF: 0.612 AC: 2948 AN: 4820

European-Finnish (FIN) AF: 0.622 AC: 6544 AN: 10514

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.590 AC: 40117 AN: 67954

Other (OTH) AF: 0.579 AC: 1225 AN: 2114

Alfa AF: 0.588 Hom.: 55717

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
PhyloP100		-0.17
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: rs10776733; hg19: chr1-112107669;