rs372223975
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005343.4(HRAS):c.222C>T(p.Thr74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,613,214 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T74T) has been classified as Likely benign.
Frequency
Consequence
NM_005343.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.222C>T | p.Thr74= | synonymous_variant | 3/6 | ENST00000311189.8 | |
HRAS | NM_176795.5 | c.222C>T | p.Thr74= | synonymous_variant | 3/6 | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.222C>T | p.Thr74= | synonymous_variant | 3/6 | 1 | NM_005343.4 | P1 | |
HRAS | ENST00000417302.7 | c.222C>T | p.Thr74= | synonymous_variant | 3/6 | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152140Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251292Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135878
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461074Hom.: 0 Cov.: 34 AF XY: 0.0000385 AC XY: 28AN XY: 726856
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74326
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 29, 2016 | Variant summary: This c.222C>T variant affects a non-conserved nucleotide, resulting in synonymous amino acid change. 5/5 splice-site tools via Alamut predict that this variant does not affect normal splicing. This variant was found in 8/120992 control chromosomes from the broad and large populations of ExAC at a frequency of 0.0000661, which is more than 25 times greater than the maximal expected frequency of a pathogenic allele (0.0000025) in this gene, showing that this variant is benign. One internal sample undergoing for NSRD testing also carried a pathogenic variant in PTPN11 p.Met504Val, further supporting the benign outcome. Taken together, this variant has been classified as Benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2020 | - - |
Costello syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at