1-111697430-TG-T

Position:

• chr1-111697430-TG-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002884.4(RAP1A):​c.127-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAP1A NM_002884.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-111697430-TG-T is Benign according to our data. Variant chr1-111697430-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 723561.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	c.127-10del		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	c.127-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000206 AC: 30 AN: 1458476 Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12 AN XY: 725614

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.000226

Gnomad4 ASJ exome AF: 0.0000769

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.00000900

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Alfa AF: 0.000359 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs1571569845; hg19: chr1-112240052; COSMIC: COSV104423181;