9-131595877-C-T

Variant names:

• chr9-131595877-C-T
• rs875968
• NM_001377935.1:c.2689+421G>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.2689+421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,130 control chromosomes in the GnomAD database, including 6,717 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 0.27 (6717 hom., cov: 33)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.2689+421G>A		intron_variant	Intron 17 of 26	ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.2689+421G>A		intron_variant	Intron 17 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.2131+421G>A		intron_variant	Intron 14 of 23	1		ENSP00000361263.2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40981 AN: 152012 Hom.: 6719 Cov.: 33

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.269 AC: 40990 AN: 152130 Hom.: 6717 Cov.: 33 AF XY: 0.270 AC XY: 20101 AN XY: 74374

African (AFR) AF: 0.0791 AC: 3283 AN: 41522

American (AMR) AF: 0.249 AC: 3816 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3470

East Asian (EAS) AF: 0.181 AC: 937 AN: 5188

South Asian (SAS) AF: 0.306 AC: 1477 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4006 AN: 10556

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25041 AN: 67960

Other (OTH) AF: 0.289 AC: 612 AN: 2114

Alfa AF: 0.336 Hom.: 7797

Bravo AF: 0.247

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.049
DANN	Benign	0.58
PhyloP100		-2.3
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: rs875968; hg19: chr9-134471264;