rs727504614
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_005343.4(HRAS):c.45C>T(p.Gly15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G15G) has been classified as Likely benign.
Frequency
Consequence
NM_005343.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.45C>T | p.Gly15= | synonymous_variant | 2/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.45C>T | p.Gly15= | synonymous_variant | 2/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.45C>T | p.Gly15= | synonymous_variant | 2/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.45C>T | p.Gly15= | synonymous_variant | 2/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250414Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135688
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461098Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21AN XY: 726912
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 16, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 04, 2013 | Gly15Gly in exon 2 of HRAS: This variant has not been previously described in th e literature and has not been identified in large population studies. However, t his variant is not expected to have clinical significance because it does not al ter an amino acid residue. In addition, this variant was identified in an unaffe cted parent of a proband. In summary, the Gly15Gly variant is likely benign. - |
HRAS-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 18, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 03, 2017 | Variant summary: The HRAS c.45C>T (p.Gly15Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation Taster predicts a damaging outcome for this variant. 4/5 splice prediction tools via Alamut predict the variant to create a cryptic splice donor site, however these predictions have not been confirmed by functional studies. This variant is absent in 120088 control chromosomes from ExAC, however, it could still be a rare polymorphism. This is supported by its presence in a new database gnomAD at an allele frequency of 0.00001221 (3/245708 chromosomes). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. One internal sample carrying this variant also carries a pathogenic variant PTPN11 p.Asn308Asp, supporting a benign outcome. One clinical diagnostic laboratory has classified this variant as likely benign, citing the variant being present in their lab in an unaffected parent of a proband. Taken together, this variant is classified as Likely Benign. - |
Costello syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at