1-111704148-ATTTTTTT-ATTTTTTTTT

Variant names:

• chr1-111704148-A-ATT
• rs71078091
• NM_002884.4:c.325-180_325-179dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002884.4(RAP1A):​c.325-180_325-179dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0011 (1 hom., cov: 0)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 148 AD gene.

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.325-180_325-179dupTT		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.325-180_325-179dupTT		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.325-180_325-179dupTT		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_325-194insTT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.325-195_325-194insTT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.325-195_325-194insTT		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 147 AN: 136856 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000796

Gnomad ASJ AF: 0.000303

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.000929

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000599

Gnomad OTH AF: 0.00263

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

GnomAD4 genome AF: 0.00108 AC: 148 AN: 136872 Hom.: 1 Cov.: 0 AF XY: 0.00110 AC XY: 72 AN XY: 65642

African (AFR) AF: 0.00186 AC: 68 AN: 36628

American (AMR) AF: 0.000795 AC: 11 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.000303 AC: 1 AN: 3304

East Asian (EAS) AF: 0.00169 AC: 8 AN: 4724

South Asian (SAS) AF: 0.000933 AC: 4 AN: 4286

European-Finnish (FIN) AF: 0.00170 AC: 13 AN: 7636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000599 AC: 38 AN: 63402

Other (OTH) AF: 0.00261 AC: 5 AN: 1914

Alfa AF: 0.000127 Hom.: 113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71078091; hg19: chr1-112246770;