chr4-81448266-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152545.3(RASGEF1B):c.457G>T(p.Val153Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V153D) has been classified as Uncertain significance.
Frequency
Consequence
NM_152545.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASGEF1B | NM_152545.3 | c.457G>T | p.Val153Phe | missense_variant | 5/14 | ENST00000264400.7 | |
RASGEF1B | NM_001300735.2 | c.454G>T | p.Val152Phe | missense_variant | 5/14 | ||
RASGEF1B | NM_001300736.2 | c.331G>T | p.Val111Phe | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASGEF1B | ENST00000264400.7 | c.457G>T | p.Val153Phe | missense_variant | 5/14 | 2 | NM_152545.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251282Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135816
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460364Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726518
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.457G>T (p.V153F) alteration is located in exon 5 (coding exon 4) of the RASGEF1B gene. This alteration results from a G to T substitution at nucleotide position 457, causing the valine (V) at amino acid position 153 to be replaced by a phenylalanine (F). 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