rs11243444

Positions:

• chr9-131597867-T-C
• chr9-131597867-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377935.1(RAPGEF1):​c.2613+332A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,146 control chromosomes in the GnomAD database, including 2,065 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 0.12 (2065 hom., cov: 32)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPGEF1	NM_001377935.1	c.2613+332A>G		intron_variant		ENST00000683357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.2613+332A>G		intron_variant			NM_001377935.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18607 AN: 152028 Hom.: 2063 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.123 AC: 18638 AN: 152146 Hom.: 2065 Cov.: 32 AF XY: 0.123 AC XY: 9146 AN XY: 74372

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0316

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0454 Hom.: 96

Bravo AF: 0.140

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.076
DANN	Benign	0.65

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: rs11243444; hg19: chr9-134473254;