rs11243445

Variant names:

• chr9-131597884-C-G
• rs11243445
• NM_001377935.1:c.2613+315G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.2613+315G>C		intron_variant	Intron 16 of 26	ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.2613+315G>C		intron_variant	Intron 16 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.2055+315G>C		intron_variant	Intron 13 of 23	1		ENSP00000361263.2

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

African (AFR) AF: 0.181 AC: 7505 AN: 41512

American (AMR) AF: 0.0382 AC: 585 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3470

East Asian (EAS) AF: 0.0885 AC: 459 AN: 5184

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4820

European-Finnish (FIN) AF: 0.0129 AC: 137 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1373 AN: 68014

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

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
PhyloP100		0.25
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: rs11243445; hg19: chr9-134473271;