1-111695324-CTT-CTTTT

Variant names:

• chr1-111695324-C-CTT
• NM_002884.4:c.58-9_58-8dupTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_002884.4(RAP1A):​c.58-9_58-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,314,582 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: RAP1A NM_002884.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.58-9_58-8dupTT		splice_region_variant, intron_variant	Intron 2 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.58-17_58-16insTT		intron_variant	Intron 2 of 7	1	NM_002884.4	ENSP00000358723.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000380 AC: 5 AN: 1314582 Hom.: 0 Cov.: 28 AF XY: 0.00000153 AC XY: 1 AN XY: 655534

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000360

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000294

Gnomad4 OTH exome AF: 0.0000185

GnomAD4 genome Cov.: 32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-112237946;