1-111658706-A-G

Variant names:

• chr1-111658706-A-G
• rs571020
• NM_002884.4:c.-27-32628A>G

Variant summary

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

The NM_002884.4(RAP1A):​c.-27-32628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,218 control chromosomes in the GnomAD database, including 1,460 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 0.12 (1460 hom., cov: 32)
• Consequence: RAP1A NM_002884.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.-27-32628A>G		intron_variant	Intron 1 of 7	ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.-27-32628A>G		intron_variant	Intron 1 of 7	1	NM_002884.4	ENSP00000358723.3
RAP1A	ENST00000356415.5	c.-27-32628A>G		intron_variant	Intron 1 of 7	1		ENSP00000348786.1
RAP1A	ENST00000687939.1	c.-28+31143A>G		intron_variant	Intron 2 of 8			ENSP00000509234.1
RAP1A	ENST00000494982.1	n.91+31147A>G		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18335 AN: 152100 Hom.: 1462 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.120 AC: 18327 AN: 152218 Hom.: 1460 Cov.: 32 AF XY: 0.124 AC XY: 9259 AN XY: 74416

African (AFR) AF: 0.0350 AC: 1453 AN: 41564

American (AMR) AF: 0.183 AC: 2793 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1088 AN: 5182

South Asian (SAS) AF: 0.115 AC: 553 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2159 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9373 AN: 67980

Other (OTH) AF: 0.130 AC: 274 AN: 2114

Alfa AF: 0.145 Hom.: 316

Bravo AF: 0.118

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.40
PhyloP100		0.53
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: rs571020; hg19: chr1-112201328;