chr9-131614993-C-T

Variant names:

• chr9-131614993-C-T
• rs1544305
• NM_001377935.1:c.2061+4058G>A

Variant summary

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

The NM_001377935.1(RAPGEF1):​c.2061+4058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,300 control chromosomes in the GnomAD database, including 57,831 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 0.87 (57831 hom., cov: 34)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	NM_001377935.1	MANE Select	c.2061+4058G>A		intron	N/A	NP_001364864.1
	RAPGEF1	NM_001377938.1		c.1950+4058G>A		intron	N/A	NP_001364867.1
	RAPGEF1	NM_198679.2		c.1908+6803G>A		intron	N/A	NP_941372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	ENST00000683357.1	MANE Select	c.2061+4058G>A		intron	N/A	ENSP00000508246.1
	RAPGEF1	ENST00000372190.8	TSL:1	c.1908+6803G>A		intron	N/A	ENSP00000361264.3
	RAPGEF1	ENST00000372195.5	TSL:1	c.1905+6803G>A		intron	N/A	ENSP00000361269.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132290 AN: 152182 Hom.: 57771 Cov.: 34

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.869 AC: 132407 AN: 152300 Hom.: 57831 Cov.: 34 AF XY: 0.874 AC XY: 65112 AN XY: 74474

African (AFR) AF: 0.947 AC: 39359 AN: 41570

American (AMR) AF: 0.826 AC: 12637 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2856 AN: 3472

East Asian (EAS) AF: 0.841 AC: 4361 AN: 5186

South Asian (SAS) AF: 0.819 AC: 3951 AN: 4824

European-Finnish (FIN) AF: 0.925 AC: 9822 AN: 10614

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

European-Non Finnish (NFE) AF: 0.832 AC: 56619 AN: 68022

Other (OTH) AF: 0.844 AC: 1784 AN: 2114

Alfa AF: 0.844 Hom.: 5811

Bravo AF: 0.863

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.68
PhyloP100		-1.2
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: rs1544305; hg19: chr9-134490380;