Variant 1-111695293-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002884.4(RAP1A):c.58-48A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,378,354 control chromosomes in the GnomAD database, including 85,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7686 hom., cov: 32)

Exomes 𝑓: 0.35 ( 77742 hom. )

Consequence

RAP1A
NM_002884.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.120

Variant links:

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]

RAP1A links:

INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

INKA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-111695293-A-T is Benign according to our data. Variant chr1-111695293-A-T is described in ClinVar as [Benign]. Clinvar id is 1246461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_002884.4 linkuse as main transcript	c.58-48A>T		intron_variant		ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4 linkuse as main transcript	c.58-48A>T		intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47286

AN:

151864

Hom.:

7687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.346

AC:

57276

AN:

165440

Hom.:

10110

AF XY:

0.353

AC XY:

32586

AN XY:

92282

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.353

AC:

432667

AN:

1226372

Hom.:

77742

Cov.:

AF XY:

0.354

AC XY:

218433

AN XY:

616178

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.355

GnomAD4 genome

AF:

0.311

AC:

47284

AN:

151982

Hom.:

7686

Cov.:

AF XY:

0.313

AC XY:

23260

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.353

Gnomad4 ASJ

AF:

0.363

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.332

Alfa

AF:

0.329

Hom.:

1566

Bravo

AF:

0.312

Asia WGS

AF:

0.373

AC:

1289

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over