1-111583091-A-G

Position:

• chr1-111583091-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_001370216.2	c.-28+40582A>G		intron_variant			NP_001357145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000356415.5	c.-28+40582A>G		intron_variant		1		ENSP00000348786	P1

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.821

Alfa AF: 0.849 Hom.: 7666

Bravo AF: 0.774

Asia WGS AF: 0.862 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.77
DANN	Benign	0.37

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: rs10494136; hg19: chr1-112125713;