1-111704148-ATTTTTTT-ATTTTTTTTTT

Variant names:

• chr1-111704148-A-ATTT
• rs71078091
• NM_002884.4:c.325-181_325-179dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002884.4(RAP1A):​c.325-181_325-179dupTTT 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 0.047 (161 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0714 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.325-181_325-179dupTTT		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.325-181_325-179dupTTT		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.325-181_325-179dupTTT		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_325-194insTTT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.325-195_325-194insTTT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.325-195_325-194insTTT		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 6432 AN: 136778 Hom.: 160 Cov.: 0

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0443

Gnomad MID AF: 0.0445

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0426

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

GnomAD4 genome AF: 0.0470 AC: 6426 AN: 136794 Hom.: 161 Cov.: 0 AF XY: 0.0464 AC XY: 3043 AN XY: 65578

African (AFR) AF: 0.0404 AC: 1480 AN: 36610

American (AMR) AF: 0.0334 AC: 462 AN: 13816

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 175 AN: 3302

East Asian (EAS) AF: 0.0102 AC: 48 AN: 4722

South Asian (SAS) AF: 0.0783 AC: 335 AN: 4278

European-Finnish (FIN) AF: 0.0443 AC: 337 AN: 7612

Middle Eastern (MID) AF: 0.0448 AC: 12 AN: 268

European-Non Finnish (NFE) AF: 0.0528 AC: 3347 AN: 63394

Other (OTH) AF: 0.0418 AC: 80 AN: 1912

Alfa AF: 0.0140 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;