2-130931121-CT-TC

Variant names:

• chr2-130931121-CT-TC
• NM_001367493.1:c.3722_3723delCTinsTC
• ARHGEF4 p.Pro1241Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001367493.1(ARHGEF4):​c.3722_3723delCTinsTC​(p.Pro1241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGEF4 NM_001367493.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 0 publications found

Genes affected

ARHGEF4 (HGNC:684): (Rho guanine nucleotide exchange factor 4) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The protein encoded by this gene may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367493.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF4	NM_001367493.1	MANE Select	c.3722_3723delCTinsTC	p.Pro1241Leu	missense	N/A	NP_001354422.1	E7EV07
	ARHGEF4	NM_001375900.1		c.209_210delCTinsTC	p.Pro70Leu	missense	N/A	NP_001362829.1
	ARHGEF4	NM_015320.4		c.164_165delCTinsTC	p.Pro55Leu	missense	N/A	NP_056135.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF4	ENST00000409359.7	TSL:5 MANE Select	c.3722_3723delCTinsTC	p.Pro1241Leu	missense	N/A	ENSP00000386794.3	E7EV07
	ARHGEF4	ENST00000392953.8	TSL:1	c.236_237delCTinsTC	p.Pro79Leu	missense	N/A	ENSP00000376680.5	A0A0C4DFY6
	ARHGEF4	ENST00000918336.1		c.3722_3723delCTinsTC	p.Pro1241Leu	missense	N/A	ENSP00000588395.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-131688694;