1-111695209-A-ATAATAT

Position:

• chr1-111695209-A-ATAATAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002884.4(RAP1A):​c.58-130_58-129insATATTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 554,798 control chromosomes in the GnomAD database, including 202,975 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54851 hom., cov: 0)
  • Exomes 𝑓: 0.85 (148124 hom.)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 -10 ACMG points.

• BP6: Variant 1-111695209-A-ATAATAT is Benign according to our data. Variant chr1-111695209-A-ATAATAT is described in ClinVar as [Benign]. Clinvar id is 1240525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.58-130_58-129insATATTA		intron_variant		ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.58-130_58-129insATATTA		intron_variant		1	NM_002884.4	ENSP00000358723	P1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 128756 AN: 151492 Hom.: 54815 Cov.: 0

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.854 AC: 344269 AN: 403188 Hom.: 148124 AF XY: 0.856 AC XY: 186688 AN XY: 218156

Gnomad4 AFR exome AF: 0.775

Gnomad4 AMR exome AF: 0.897

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.850 AC: 128849 AN: 151610 Hom.: 54851 Cov.: 0 AF XY: 0.853 AC XY: 63146 AN XY: 74060

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.846

Alfa AF: 0.772 Hom.: 1491

Asia WGS AF: 0.955 AC: 3288 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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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: rs3085873; hg19: chr1-112237831;