chr1-111658706-A-G

Position:

• chr1-111658706-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369709.4(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 ENST00000369709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RAP1A	NM_002884.4	c.-27-32628A>G		intron_variant		ENST00000369709.4	NP_002875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1A	ENST00000369709.4	c.-27-32628A>G		intron_variant		1	NM_002884.4	ENSP00000358723	P1
RAP1A	ENST00000356415.5	c.-27-32628A>G		intron_variant		1		ENSP00000348786	P1
RAP1A	ENST00000687939.1	c.-28+31143A>G		intron_variant				ENSP00000509234	P1
RAP1A	ENST00000494982.1	n.91+31147A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0350

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.130

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

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: rs571020; hg19: chr1-112201328;