1-111624633-T-C

Variant names:

• chr1-111624633-T-C
• rs530801
• NM_002884.4:c.-28+4699T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002884.4(RAP1A):​c.-28+4699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,084 control chromosomes in the GnomAD database, including 57,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57360 hom., cov: 31)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 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.-28+4699T>C		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.-121-2837T>C		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.-28+4286T>C		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.-28+4699T>C		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.-27-66701T>C		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.-121-2837T>C		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131698 AN: 151966 Hom.: 57299 Cov.: 31

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.867 AC: 131820 AN: 152084 Hom.: 57360 Cov.: 31 AF XY: 0.863 AC XY: 64154 AN XY: 74310

African (AFR) AF: 0.923 AC: 38316 AN: 41498

American (AMR) AF: 0.812 AC: 12412 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4080 AN: 5166

South Asian (SAS) AF: 0.886 AC: 4278 AN: 4826

European-Finnish (FIN) AF: 0.798 AC: 8404 AN: 10534

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58468 AN: 67986

Other (OTH) AF: 0.860 AC: 1817 AN: 2114

Alfa AF: 0.816 Hom.: 4771

Bravo AF: 0.868

Asia WGS AF: 0.831 AC: 2890 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs530801; hg19: chr1-112167255;