1-111583091-A-G

Variant names:

• chr1-111583091-A-G
• rs10494136
• ENST00000356415.5:c.-28+40582A>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+40582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,032 control chromosomes in the GnomAD database, including 50,346 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 0.79 (50346 hom., cov: 30)
• Consequence: RAP1A ENST00000356415.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356415.5. 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_001370216.2		c.-28+40582A>G		intron	N/A	NP_001357145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	ENST00000356415.5	TSL:1	c.-28+40582A>G		intron	N/A	ENSP00000348786.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120145 AN: 151914 Hom.: 50346 Cov.: 30

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.790 AC: 120181 AN: 152032 Hom.: 50346 Cov.: 30 AF XY: 0.796 AC XY: 59128 AN XY: 74308

African (AFR) AF: 0.483 AC: 19968 AN: 41346

American (AMR) AF: 0.900 AC: 13756 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3074 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4565 AN: 5184

South Asian (SAS) AF: 0.853 AC: 4106 AN: 4812

European-Finnish (FIN) AF: 0.943 AC: 9985 AN: 10586

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61923 AN: 68024

Other (OTH) AF: 0.821 AC: 1736 AN: 2114

Alfa AF: 0.868 Hom.: 27816

Bravo AF: 0.774

Asia WGS AF: 0.862 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.77
DANN	Benign	0.37
PhyloP100		-0.35
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: rs10494136; hg19: chr1-112125713;