NM_001377935.1:c.61+18482A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377935.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	NM_001377935.1	MANE Select	c.61+18482A>G		intron	N/A	NP_001364864.1
	RAPGEF1	NM_001377938.1		c.61+18482A>G		intron	N/A	NP_001364867.1
	RAPGEF1	NM_001304275.2		c.61+18482A>G		intron	N/A	NP_001291204.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF1	ENST00000683357.1	MANE Select	c.61+18482A>G		intron	N/A	ENSP00000508246.1
	RAPGEF1	ENST00000372195.5	TSL:1	c.61+18482A>G		intron	N/A	ENSP00000361269.1
	RAPGEF1	ENST00000372189.7	TSL:1	c.10+16117A>G		intron	N/A	ENSP00000361263.2

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

African (AFR) AF: 0.617 AC: 25586 AN: 41440

American (AMR) AF: 0.718 AC: 10952 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2543 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4014 AN: 5178

South Asian (SAS) AF: 0.744 AC: 3584 AN: 4818

European-Finnish (FIN) AF: 0.843 AC: 8927 AN: 10592

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55672 AN: 67984

Other (OTH) AF: 0.728 AC: 1541 AN: 2116

Alfa AF: 0.755 Hom.: 24674

Bravo AF: 0.729

Asia WGS AF: 0.752 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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