1-111704148-ATTTTTTT-ATTTTTT

Variant names:

• chr1-111704148-AT-A
• rs71078091
• NM_002884.4:c.325-179delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency: Genomes: 𝑓 0.30 (5696 hom., cov: 0)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-111704148-AT-A is Benign according to our data. Variant chr1-111704148-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1288197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002884.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	NM_002884.4	MANE Select	c.325-179delT		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.325-179delT		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.325-179delT		intron	N/A	NP_001278825.1	P62834

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	ENST00000369709.4	TSL:1 MANE Select	c.325-194delT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.325-194delT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.325-194delT		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.299 AC: 40930 AN: 136710 Hom.: 5690 Cov.: 0

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.300 AC: 40958 AN: 136728 Hom.: 5696 Cov.: 0 AF XY: 0.300 AC XY: 19647 AN XY: 65578

African (AFR) AF: 0.442 AC: 16157 AN: 36594

American (AMR) AF: 0.253 AC: 3502 AN: 13816

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 805 AN: 3300

East Asian (EAS) AF: 0.281 AC: 1326 AN: 4714

South Asian (SAS) AF: 0.245 AC: 1049 AN: 4278

European-Finnish (FIN) AF: 0.310 AC: 2370 AN: 7640

Middle Eastern (MID) AF: 0.156 AC: 42 AN: 270

European-Non Finnish (NFE) AF: 0.237 AC: 14999 AN: 63324

Other (OTH) AF: 0.289 AC: 552 AN: 1912

Alfa AF: 0.112 Hom.: 113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71078091; hg19: chr1-112246770; COSMIC: COSV62729303;