9-131614993-C-T

Position:

• chr9-131614993-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.2061+4058G>A		intron_variant		ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.2061+4058G>A		intron_variant			NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.1854+6803G>A		intron_variant		1		ENSP00000361263.2

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

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.844

Alfa AF: 0.839 Hom.: 5468

Bravo AF: 0.863

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.68

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: rs1544305; hg19: chr9-134490380;