1-111697229-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002884.4(RAP1A):c.127-212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,022 control chromosomes in the GnomAD database, including 7,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7346 hom., cov: 32)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-111697229-C-T is Benign according to our data. Variant chr1-111697229-C-T is described in ClinVar as [Benign]. Clinvar id is 1222792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1A	NM_002884.4	c.127-212C>T		intron_variant		ENST00000369709.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1A	ENST00000369709.4	c.127-212C>T		intron_variant		1	NM_002884.4	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45309 AN: 151904 Hom.: 7346 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.298 AC: 45306 AN: 152022 Hom.: 7346 Cov.: 32 AF XY: 0.301 AC XY: 22346 AN XY: 74302

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.320

Alfa AF: 0.303 Hom.: 901

Bravo AF: 0.296

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.2
Dann	Benign	0.77

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: rs2365323; hg19: chr1-112239851;