1-111697416-C-CT

Position:

• chr1-111697416-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002884.4(RAP1A):​c.127-11dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,552,866 control chromosomes in the GnomAD database, including 4,477 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4459 hom., cov: 22)
  • Exomes 𝑓: 0.16 (18 hom.)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.159

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 -10 ACMG points.

• BP6: Variant 1-111697416-C-CT is Benign according to our data. Variant chr1-111697416-C-CT is described in ClinVar as [Benign]. Clinvar id is 1253450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.127-11dup		intron_variant		ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.127-11dup		intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 34343 AN: 142388 Hom.: 4449 Cov.: 22

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.161 AC: 227013 AN: 1410432 Hom.: 18 Cov.: 0 AF XY: 0.158 AC XY: 110598 AN XY: 701854

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.0940

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.241 AC: 34377 AN: 142434 Hom.: 4459 Cov.: 22 AF XY: 0.239 AC XY: 16547 AN XY: 69120

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.225

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

Jun 02, 2021

- -

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: rs34219774; hg19: chr1-112240038;