rs752090

Variant names:

• chr9-131674641-C-T
• rs752090
• NM_001377935.1:c.62-23692G>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.62-23692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,194 control chromosomes in the GnomAD database, including 669 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 0.087 (669 hom., cov: 32)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.62-23692G>A		intron_variant	Intron 1 of 26	ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.62-23692G>A		intron_variant	Intron 1 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372189.7	c.11-23692G>A		intron_variant	Intron 1 of 23	1		ENSP00000361263.2

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13276 AN: 152076 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0873 AC: 13283 AN: 152194 Hom.: 669 Cov.: 32 AF XY: 0.0872 AC XY: 6486 AN XY: 74406

African (AFR) AF: 0.0939 AC: 3896 AN: 41508

American (AMR) AF: 0.0832 AC: 1272 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3466

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.115 AC: 556 AN: 4816

European-Finnish (FIN) AF: 0.0627 AC: 664 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5889 AN: 68024

Other (OTH) AF: 0.109 AC: 230 AN: 2112

Alfa AF: 0.0839 Hom.: 78

Bravo AF: 0.0893

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.70
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: rs752090; hg19: chr9-134550028;