13-77975416-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000115.5(EDNRB):c.-121G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,200 control chromosomes in the GnomAD database, including 5,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_000115.5 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OBI1-AS1 | ENST00000607862.5 | n.230+55498C>A | intron_variant | Intron 1 of 2 | 1 | |||||
EDNRB | ENST00000646948.1 | c.-121G>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 8 | ENSP00000493895.1 | |||||
EDNRB | ENST00000646948.1 | c.-121G>T | 5_prime_UTR_variant | Exon 1 of 8 | ENSP00000493895.1 |
Frequencies
GnomAD3 genomes AF: 0.248 AC: 37665AN: 151960Hom.: 5823 Cov.: 32
GnomAD4 exome AF: 0.197 AC: 24AN: 122Hom.: 2 Cov.: 0 AF XY: 0.181 AC XY: 17AN XY: 94
GnomAD4 genome AF: 0.248 AC: 37738AN: 152078Hom.: 5848 Cov.: 32 AF XY: 0.251 AC XY: 18687AN XY: 74356
ClinVar
Submissions by phenotype
Hirschsprung disease, susceptibility to, 2 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at