NM_001377935.1:c.2613+565G>C

Variant names:

• chr9-131597634-C-G
• rs4740294
• NM_001377935.1:c.2613+565G>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+565G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,222 control chromosomes in the GnomAD database, including 53,636 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 0.84 (53636 hom., cov: 33)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377935.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	NM_001377935.1	MANE Select	c.2613+565G>C		intron	N/A	NP_001364864.1
	RAPGEF1	NM_001377938.1		c.2502+565G>C		intron	N/A	NP_001364867.1
	RAPGEF1	NM_198679.2		c.2109+565G>C		intron	N/A	NP_941372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	ENST00000683357.1	MANE Select	c.2613+565G>C		intron	N/A	ENSP00000508246.1
	RAPGEF1	ENST00000372190.8	TSL:1	c.2109+565G>C		intron	N/A	ENSP00000361264.3
	RAPGEF1	ENST00000372195.5	TSL:1	c.2106+565G>C		intron	N/A	ENSP00000361269.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127562 AN: 152104 Hom.: 53589 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.839 AC: 127666 AN: 152222 Hom.: 53636 Cov.: 33 AF XY: 0.842 AC XY: 62643 AN XY: 74430

African (AFR) AF: 0.875 AC: 36324 AN: 41534

American (AMR) AF: 0.837 AC: 12803 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2845 AN: 3466

East Asian (EAS) AF: 0.795 AC: 4108 AN: 5170

South Asian (SAS) AF: 0.834 AC: 4023 AN: 4826

European-Finnish (FIN) AF: 0.870 AC: 9224 AN: 10608

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55553 AN: 68004

Other (OTH) AF: 0.834 AC: 1764 AN: 2116

Alfa AF: 0.837 Hom.: 6606

Bravo AF: 0.837

Asia WGS AF: 0.833 AC: 2896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-1.0
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: rs4740294; hg19: chr9-134473021;