Variant 1-111704148-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002884.4(RAP1A):c.325-179dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1262 hom., cov: 0)

Consequence

RAP1A
NM_002884.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246

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 -10 ACMG points.

BP6

Variant 1-111704148-A-AT is Benign according to our data. Variant chr1-111704148-A-AT is described in ClinVar as [Benign]. Clinvar id is 1182895.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.325-179dup		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.325-179dup		intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

16366

AN:

136786

Hom.:

1263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.0261

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.129

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

GnomAD4 genome

AF:

0.120

AC:

16357

AN:

136804

Hom.:

1262

Cov.:

AF XY:

0.121

AC XY:

7951

AN XY:

65604

show subpopulations

Gnomad4 AFR

AF:

0.0368

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing