1-111663769-T-C

Variant names:

• chr1-111663769-T-C
• rs575208
• NM_002884.4:c.-27-27565T>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.-27-27565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,016 control chromosomes in the GnomAD database, including 17,743 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 0.48 (17743 hom., cov: 31)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 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.-27-27565T>C		intron	N/A	NP_002875.1	P62834
	RAP1A	NM_001010935.3		c.-27-27565T>C		intron	N/A	NP_001010935.1	P62834
	RAP1A	NM_001291896.3		c.-27-27565T>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.-27-27565T>C		intron	N/A	ENSP00000358723.3	P62834
	RAP1A	ENST00000356415.5	TSL:1	c.-27-27565T>C		intron	N/A	ENSP00000348786.1	P62834
	RAP1A	ENST00000687939.1		c.-27-27565T>C		intron	N/A	ENSP00000509234.1	P62834

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72719 AN: 151898 Hom.: 17701 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.479 AC: 72814 AN: 152016 Hom.: 17743 Cov.: 31 AF XY: 0.481 AC XY: 35743 AN XY: 74314

African (AFR) AF: 0.558 AC: 23128 AN: 41436

American (AMR) AF: 0.471 AC: 7203 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2609 AN: 5180

South Asian (SAS) AF: 0.431 AC: 2078 AN: 4822

European-Finnish (FIN) AF: 0.546 AC: 5765 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29003 AN: 67942

Other (OTH) AF: 0.461 AC: 975 AN: 2114

Alfa AF: 0.446 Hom.: 8537

Bravo AF: 0.479

Asia WGS AF: 0.524 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.56
PhyloP100		-0.092
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: rs575208; hg19: chr1-112206391;