1-111704148-ATTTTTTT-ATTTTTTTTTTT

Variant names:

• chr1-111704148-A-ATTTT
• rs71078091
• NM_002884.4:c.325-182_325-179dupTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002884.4(RAP1A):​c.325-182_325-179dupTTTT 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 0.00015 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.325-182_325-179dupTTTT		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_325-194insTTTT		intron_variant	Intron 5 of 7	1	NM_002884.4	ENSP00000358723.3

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 21 AN: 136866 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000219

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000464

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000126

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000146 AC: 20 AN: 136882 Hom.: 0 Cov.: 0 AF XY: 0.000137 AC XY: 9 AN XY: 65646

Gnomad4 AFR AF: 0.000191

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000466

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000126

Gnomad4 OTH AF: 0.00

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;