rs4991743

Variant names:

• chr9-131732360-A-G
• rs4991743
• NM_001377935.1:c.61+7410T>C

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 4 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=-0.87).
• 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 rank	MANE	Protein	UniProt
RAPGEF1	NM_001377935.1	c.61+7410T>C		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+7410T>C		intron_variant	Intron 1 of 26		NM_001377935.1	ENSP00000508246.1
RAPGEF1	ENST00000372195.5	c.61+7410T>C		intron_variant	Intron 1 of 23	1		ENSP00000361269.1
RAPGEF1	ENST00000372189.7	c.10+5045T>C		intron_variant	Intron 1 of 23	1		ENSP00000361263.2
RAPGEF1	ENST00000438647.3	c.61+7410T>C		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.954 AC: 39663 AN: 41568

American (AMR) AF: 0.862 AC: 13184 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3117 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4364 AN: 5184

South Asian (SAS) AF: 0.850 AC: 4097 AN: 4822

European-Finnish (FIN) AF: 0.934 AC: 9905 AN: 10608

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59527 AN: 68014

Other (OTH) AF: 0.884 AC: 1867 AN: 2112

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
PhyloP100		-0.098
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: rs4991743; hg19: chr9-134607747;