NM_001367493.1:c.4126C>G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001367493.1(ARHGEF4):c.4126C>G(p.Leu1376Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000997 in 1,604,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001367493.1 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF4 | NM_001367493.1 | c.4126C>G | p.Leu1376Val | missense_variant, splice_region_variant | Exon 6 of 14 | ENST00000409359.7 | NP_001354422.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245806Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133178
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1452050Hom.: 0 Cov.: 31 AF XY: 0.00000971 AC XY: 7AN XY: 721220
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.568C>G (p.L190V) alteration is located in exon 6 (coding exon 4) of the ARHGEF4 gene. This alteration results from a C to G substitution at nucleotide position 568, causing the leucine (L) at amino acid position 190 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at