rs4991743

Positions:

• chr9-131732360-A-G
• chr9-131732360-A-T

Variant summary

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

The NM_001377935.1(RAPGEF1):​c.61+7410T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,286 control chromosomes in the GnomAD database, including 61,591 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 0.90 (61591 hom., cov: 33)
• Consequence: RAPGEF1 NM_001377935.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.61+7410T>C		intron_variant		ENST00000683357.1	NP_001364864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPGEF1	ENST00000683357.1	c.61+7410T>C		intron_variant			NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372195.5	c.61+7410T>C		intron_variant		1		ENSP00000361269.1
RAPGEF1	ENST00000372189.7	c.10+5045T>C		intron_variant		1		ENSP00000361263.2
RAPGEF1	ENST00000438647.3	c.61+7410T>C		intron_variant		3		ENSP00000410640.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136665 AN: 152168 Hom.: 61532 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.898 AC: 136781 AN: 152286 Hom.: 61591 Cov.: 33 AF XY: 0.901 AC XY: 67059 AN XY: 74458

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.884

Alfa AF: 0.881 Hom.: 9809

Bravo AF: 0.893

Asia WGS AF: 0.853 AC: 2969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4991743; hg19: chr9-134607747;