chr1-111697416-C-CTT

Variant names:

• chr1-111697416-C-CTT
• rs34219774
• NM_002884.4:c.127-12_127-11dupTT

Variant summary

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

The NM_002884.4(RAP1A):​c.127-12_127-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0009 in 1,570,240 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: 𝑓 0.0013 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00086 (0 hom.)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.127-12_127-11dupTT		intron_variant	Intron 3 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.127-25_127-24insTT		intron_variant	Intron 3 of 7	1	NM_002884.4	ENSP00000358723.3

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 180 AN: 142460 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000604

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.000236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000308

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.000864 AC: 1233 AN: 1427734 Hom.: 0 Cov.: 0 AF XY: 0.000898 AC XY: 638 AN XY: 710394

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.000910

Gnomad4 EAS exome AF: 0.000717

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.000987

Gnomad4 NFE exome AF: 0.000658

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00127 AC: 181 AN: 142506 Hom.: 0 Cov.: 22 AF XY: 0.00145 AC XY: 100 AN XY: 69162

Gnomad4 AFR AF: 0.00353

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000606

Gnomad4 SAS AF: 0.000224

Gnomad4 FIN AF: 0.000236

Gnomad4 NFE AF: 0.000308

Gnomad4 OTH AF: 0.00102

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: rs34219774; hg19: chr1-112240038;