9-131721288-T-C

Variant names:

• chr9-131721288-T-C
• rs10901081
• NM_001377935.1:c.61+18482A>G

Variant summary

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

The NM_001377935.1(RAPGEF1):​c.61+18482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,054 control chromosomes in the GnomAD database, including 43,141 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 0.75 (43141 hom., cov: 31)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.61+18482A>G		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.61+18482A>G		intron_variant	Intron 1 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372195.5	c.61+18482A>G		intron_variant	Intron 1 of 23	1		ENSP00000361269.1
RAPGEF1	ENST00000372189.7	c.10+16117A>G		intron_variant	Intron 1 of 23	1		ENSP00000361263.2
RAPGEF1	ENST00000438647.3	c.61+18482A>G		intron_variant	Intron 1 of 3	3		ENSP00000410640.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113603 AN: 151938 Hom.: 43115 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.748 AC: 113685 AN: 152054 Hom.: 43141 Cov.: 31 AF XY: 0.750 AC XY: 55704 AN XY: 74318

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.728

Alfa AF: 0.781 Hom.: 18719

Bravo AF: 0.729

Asia WGS AF: 0.752 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10901081; hg19: chr9-134596675; COSMIC: COSV64698659; COSMIC: COSV64698659;