rs747854581
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_005343.4(HRAS):c.290+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,042 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 (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
HRAS
NM_005343.4 intron
NM_005343.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.80
Genes affected
HRAS (HGNC:5173): (HRas proto-oncogene, GTPase) This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 11-533757-G-A is Benign according to our data. Variant chr11-533757-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462150.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.290+9C>T | intron_variant | ENST00000311189.8 | |||
HRAS | NM_176795.5 | c.290+9C>T | intron_variant | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.290+9C>T | intron_variant | 1 | NM_005343.4 | P1 | |||
HRAS | ENST00000417302.7 | c.290+9C>T | intron_variant | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250986Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135796
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460872Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 726760
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74332
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Costello syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at