Variant 1-111697431-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_002884.4(RAP1A):c.127-10G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAP1A
NM_002884.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001279

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.988

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-111697431-G-T is Benign according to our data. Variant chr1-111697431-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 769526.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_002884.4 linkuse as main transcript	c.127-10G>T		splice_polypyrimidine_tract_variant, 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.127-10G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

154

AN:

117652

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000829

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00658

Gnomad MID

AF:

0.00403

Gnomad NFE

AF:

0.000815

Gnomad OTH

AF:

0.00187

GnomAD3 exomes

AF:

0.00472

AC:

680

AN:

144188

Hom.:

AF XY:

0.00449

AC XY:

349

AN XY:

77706

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00758

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00352

Gnomad SAS exome

AF:

0.00660

Gnomad FIN exome

AF:

0.00785

Gnomad NFE exome

AF:

0.00326

Gnomad OTH exome

AF:

0.00581

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00120

AC:

1621

AN:

1352250

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

798

AN XY:

669726

show subpopulations

Gnomad4 AFR exome

AF:

0.00415

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.00266

Gnomad4 EAS exome

AF:

0.000385

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.00423

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00132

AC:

155

AN:

117702

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

AN XY:

56990

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.000827

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00658

Gnomad4 NFE

AF:

0.000815

Gnomad4 OTH

AF:

0.00246

Alfa

AF:

0.00427

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.090

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.0

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