chr11-534197-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005343.4(HRAS):c.111+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,589,506 control chromosomes in the GnomAD database, including 3,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_005343.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0478 AC: 7270AN: 152158Hom.: 336 Cov.: 33
GnomAD3 exomes AF: 0.0739 AC: 18380AN: 248758Hom.: 1163 AF XY: 0.0709 AC XY: 9574AN XY: 135030
GnomAD4 exome AF: 0.0546 AC: 78409AN: 1437228Hom.: 3120 Cov.: 28 AF XY: 0.0551 AC XY: 39480AN XY: 716572
GnomAD4 genome AF: 0.0478 AC: 7274AN: 152278Hom.: 337 Cov.: 33 AF XY: 0.0500 AC XY: 3725AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:7
c.111+15G>A in Intron 02 of HRAS: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 4.1% (291/7016) of European American chromosomes from a b road population by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS; dbSNP rs41258054). -
Variant summary: HRAS c.111+15G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.074 in 248758 control chromosomes, predominantly at a frequency of 0.19 within the Latino subpopulation in the gnomAD database, including 688 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 80000-folds over the estimated maximal expected allele frequency for a pathogenic variant in HRAS causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
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not provided Benign:3
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Costello syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at