1-111695209-A-ATAATAT

Variant names:

• chr1-111695209-A-ATAATAT
• rs3085873
• NM_002884.4:c.58-130_58-129insATATTA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002884.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	NM_002884.4	MANE Select	c.58-130_58-129insATATTA		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.58-130_58-129insATATTA		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.58-130_58-129insATATTA		intron	N/A	NP_001278825.1	P62834

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1A	ENST00000369709.4	TSL:1 MANE Select	c.58-132_58-131insTAATAT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.58-132_58-131insTAATAT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.58-132_58-131insTAATAT		intron	N/A	ENSP00000509234.1	P62834

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

African (AFR) AF: 0.775 AC: 6475 AN: 8354

American (AMR) AF: 0.897 AC: 9023 AN: 10064

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 11426 AN: 12838

East Asian (EAS) AF: 0.999 AC: 20645 AN: 20656

South Asian (SAS) AF: 0.891 AC: 32022 AN: 35948

European-Finnish (FIN) AF: 0.842 AC: 30359 AN: 36042

Middle Eastern (MID) AF: 0.870 AC: 1429 AN: 1642

European-Non Finnish (NFE) AF: 0.837 AC: 214531 AN: 256208

Other (OTH) AF: 0.856 AC: 18359 AN: 21436

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

African (AFR) AF: 0.803 AC: 33139 AN: 41278

American (AMR) AF: 0.875 AC: 13329 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3112 AN: 3464

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5190

South Asian (SAS) AF: 0.909 AC: 4385 AN: 4826

European-Finnish (FIN) AF: 0.857 AC: 8991 AN: 10486

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 57912 AN: 67818

Other (OTH) AF: 0.846 AC: 1787 AN: 2112

Alfa AF: 0.772 Hom.: 1491

Asia WGS AF: 0.955 AC: 3288 AN: 3444

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3085873; hg19: chr1-112237831; COSMIC: COSV62727589;