rs11243445

Positions:

• chr9-131597884-C-G

Variant summary

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

The NM_001377935.1(RAPGEF1):​c.2613+315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,228 control chromosomes in the GnomAD database, including 766 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 0.071 (766 hom., cov: 32)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

Genes affected

RAPGEF1 (HGNC:4568): (Rap guanine nucleotide exchange factor 1) This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.2613+315G>C		intron_variant		ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.2613+315G>C		intron_variant			NM_001377935.1	ENSP00000508246

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10752 AN: 152110 Hom.: 764 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0708 AC: 10772 AN: 152228 Hom.: 766 Cov.: 32 AF XY: 0.0699 AC XY: 5203 AN XY: 74424

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0483 Hom.: 65

Bravo AF: 0.0790

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.47

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: rs11243445; hg19: chr9-134473271;