NM_002884.4:c.325-181_325-179dupTTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.325-181_325-179dupTTT		intron_variant	Intron 5 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.325-195_325-194insTTT		intron_variant	Intron 5 of 7	1	NM_002884.4	ENSP00000358723.3

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

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0783

Gnomad4 FIN AF: 0.0443

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.0418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71078091; hg19: chr1-112246770;