chr1-111704148-ATT-A

Variant names:

• chr1-111704148-ATT-A
• rs71078091
• NM_002884.4:c.325-180_325-179delTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002884.4(RAP1A):​c.325-180_325-179delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0053 (3 hom., cov: 0)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00533 (729/136846) while in subpopulation AFR AF = 0.0177 (650/36624). AF 95% confidence interval is 0.0166. There are 3 homozygotes in GnomAd4. There are 329 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 729 AD gene.

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.325-180_325-179delTT		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.325-180_325-179delTT		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.325-180_325-179delTT		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.325-194_325-193delTT		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.325-194_325-193delTT		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.325-194_325-193delTT		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 722 AN: 136828 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00174

Gnomad ASJ AF: 0.000908

Gnomad EAS AF: 0.000633

Gnomad SAS AF: 0.000464

Gnomad FIN AF: 0.00131

Gnomad MID AF: 0.0136

Gnomad NFE AF: 0.000442

Gnomad OTH AF: 0.00315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00533 AC: 729 AN: 136846 Hom.: 3 Cov.: 0 AF XY: 0.00501 AC XY: 329 AN XY: 65620

African (AFR) AF: 0.0177 AC: 650 AN: 36624

American (AMR) AF: 0.00174 AC: 24 AN: 13824

Ashkenazi Jewish (ASJ) AF: 0.000908 AC: 3 AN: 3304

East Asian (EAS) AF: 0.000635 AC: 3 AN: 4724

South Asian (SAS) AF: 0.000466 AC: 2 AN: 4288

European-Finnish (FIN) AF: 0.00131 AC: 10 AN: 7624

Middle Eastern (MID) AF: 0.0111 AC: 3 AN: 270

European-Non Finnish (NFE) AF: 0.000442 AC: 28 AN: 63392

Other (OTH) AF: 0.00313 AC: 6 AN: 1916

Alfa AF: 0.00 Hom.: 113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs71078091; hg19: chr1-112246770;