NM_002884.4:c.325-179dupT

Variant names:

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

Variant summary

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

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

• Frequency: Genomes: 𝑓 0.12 (1262 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-A-AT is Benign according to our data. Variant chr1-111704148-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1182895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.325-179dupT		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.325-179dupT		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.325-179dupT		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.325-195_325-194insT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.325-195_325-194insT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.325-195_325-194insT		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.120 AC: 16366 AN: 136786 Hom.: 1263 Cov.: 0

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.0261

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.120 AC: 16357 AN: 136804 Hom.: 1262 Cov.: 0 AF XY: 0.121 AC XY: 7951 AN XY: 65604

African (AFR) AF: 0.0368 AC: 1347 AN: 36624

American (AMR) AF: 0.184 AC: 2543 AN: 13822

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 579 AN: 3300

East Asian (EAS) AF: 0.215 AC: 1010 AN: 4708

South Asian (SAS) AF: 0.104 AC: 445 AN: 4286

European-Finnish (FIN) AF: 0.164 AC: 1255 AN: 7630

Middle Eastern (MID) AF: 0.112 AC: 30 AN: 268

European-Non Finnish (NFE) AF: 0.140 AC: 8881 AN: 63372

Other (OTH) AF: 0.127 AC: 244 AN: 1914

Alfa AF: 0.0647 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;