chr1-111697416-CT-C

Variant names:

• chr1-111697416-CT-C
• rs34219774
• NM_002884.4:c.127-11delT

Variant summary

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

The NM_002884.4(RAP1A):​c.127-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 142,238 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 0.0027 (0 hom., cov: 22)
  • Exomes 𝑓: 0.19 (0 hom.)
  • Failed GnomAD Quality Control
• 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 386 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00270 AC: 384 AN: 142198 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000768

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.000447

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.00257

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.185 AC: 178089 AN: 961320 Hom.: 0 Cov.: 0 AF XY: 0.191 AC XY: 92721 AN XY: 485688

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.00271 AC: 386 AN: 142238 Hom.: 0 Cov.: 22 AF XY: 0.00304 AC XY: 210 AN XY: 68986

Gnomad4 AFR AF: 0.000767

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00182

Gnomad4 SAS AF: 0.000673

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.00309

Gnomad4 OTH AF: 0.00306

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;