rs748729430
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_005343.4(HRAS):c.482G>A(p.Arg161His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R161C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005343.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.482G>A | p.Arg161His | missense_variant | 5/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.*51G>A | 3_prime_UTR_variant | 6/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.482G>A | p.Arg161His | missense_variant | 5/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.*51G>A | 3_prime_UTR_variant | 6/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248716Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134938
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460760Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726702
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 14, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg161His var iant in HRAS has been identified by our laboratory in 1 individual with clinical features of RASopathy; however the variant was inherited from an unaffected par ent. This variant has also been identified in 4/18840 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSN P rs748729430). Computational prediction tools and conservation analysis suggest that the p.Arg161His variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while the clinica l significance of the p.Arg161His variant is uncertain, its identification in an unaffected individual suggests that it is more likely to be benign. ACMG/AMP cr iteria applied: BS2, PP3. - |
Costello syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 161 of the HRAS protein (p.Arg161His). This variant is present in population databases (rs748729430, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 517437). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt HRAS function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at