11-532760-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_005343.4(HRAS):c.451-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005343.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.451-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000311189.8 | |||
HRAS | NM_176795.5 | c.*20-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000417302.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.451-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005343.4 | P1 | |||
HRAS | ENST00000417302.7 | c.*20-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_176795.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247162Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134320
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459934Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726336
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74380
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2022 | The c.451-5C>T intronic alteration consists of a C to T substitution 5 nucleotides before exon 5 (coding exon 4) of the HRAS gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Costello syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at