chr1-111585096-G-A

Position:

• chr1-111585096-G-A

Variant summary

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

The ENST00000356415.5(RAP1A):​c.-28+42587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,078 control chromosomes in the GnomAD database, including 10,493 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 0.35 (10493 hom., cov: 32)
• Consequence: RAP1A ENST00000356415.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_001370216.2	c.-28+42587G>A		intron_variant			NP_001357145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000356415.5	c.-28+42587G>A		intron_variant		1		ENSP00000348786	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53113 AN: 151960 Hom.: 10486 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.349 AC: 53149 AN: 152078 Hom.: 10493 Cov.: 32 AF XY: 0.351 AC XY: 26068 AN XY: 74324

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.361

Alfa AF: 0.416 Hom.: 18622

Bravo AF: 0.330

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.52

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: rs10857899; hg19: chr1-112127718; COSMIC: COSV62726707;