1-111704148-ATTTTTTT-ATTTTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 729 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.325-180_325-179delTT		intron_variant	Intron 5 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.325-194_325-193delTT		intron_variant	Intron 5 of 7	1	NM_002884.4	ENSP00000358723.3

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

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.00174

Gnomad4 ASJ AF: 0.000908

Gnomad4 EAS AF: 0.000635

Gnomad4 SAS AF: 0.000466

Gnomad4 FIN AF: 0.00131

Gnomad4 NFE AF: 0.000442

Gnomad4 OTH AF: 0.00313

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: rs71078091; hg19: chr1-112246770;