1-111697416-CTTTTTT-CTTTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002884.4(RAP1A):​c.127-12_127-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,479,382 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 0.00046 (0 hom., cov: 22)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.828

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.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0134 (17983/1337116) while in subpopulation AMR AF= 0.0415 (1493/35940). AF 95% confidence interval is 0.0398. There are 0 homozygotes in gnomad4_exome. There are 9659 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 65 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.127-12_127-11delTT		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.127-24_127-23delTT		intron_variant	Intron 3 of 7	1	NM_002884.4	ENSP00000358723.3

Frequencies

GnomAD3 genomes AF: 0.000457 AC: 65 AN: 142220 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000424

Gnomad ASJ AF: 0.000301

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000386

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.0134 AC: 17983 AN: 1337116 Hom.: 0 AF XY: 0.0146 AC XY: 9659 AN XY: 662880

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0275

Gnomad4 EAS exome AF: 0.0223

Gnomad4 SAS exome AF: 0.0340

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.00955

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.000457 AC: 65 AN: 142266 Hom.: 0 Cov.: 22 AF XY: 0.000464 AC XY: 32 AN XY: 69016

Gnomad4 AFR AF: 0.000102

Gnomad4 AMR AF: 0.000424

Gnomad4 ASJ AF: 0.000301

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00321

Gnomad4 NFE AF: 0.000386

Gnomad4 OTH AF: 0.00102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;