rs201336064
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001201397.1(EDNRB):āc.224T>Cā(p.Leu75Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,541,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Consequence
NM_001201397.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EDNRB | NM_001122659.3 | c.-47T>C | 5_prime_UTR_variant | 1/7 | ENST00000646607.2 | NP_001116131.1 | ||
EDNRB | NM_001201397.1 | c.224T>C | p.Leu75Pro | missense_variant | 2/8 | NP_001188326.1 | ||
EDNRB | NM_000115.5 | c.-47T>C | 5_prime_UTR_variant | 2/8 | NP_000106.1 | |||
EDNRB | NM_003991.4 | c.-47T>C | 5_prime_UTR_variant | 1/7 | NP_003982.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EDNRB | ENST00000646607.2 | c.-47T>C | 5_prime_UTR_variant | 1/7 | NM_001122659.3 | ENSP00000493527.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151974Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000360 AC: 50AN: 1389848Hom.: 0 Cov.: 31 AF XY: 0.0000334 AC XY: 23AN XY: 688394
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74248
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 17, 2015 | The p.Leu75Pro variant in exon 2 of EDNRB (RefSeq ID: NM_001201397.1): This vari ant is not expected to have clinical significance because the leucine (Leu) resi due at position 75 is not conserved through species, with at least 4 mammals (da vid's myotis bat, microbat, big brown bat, shrew) having a proline (Pro) at this position. The variant has been identified in 3/75258 chromosomes from several p opulations by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs201336064). Note that the variant occurs in the predicted coding r egion of only 1 of 4 transcript isoforms of the EDNRB gene, and lies in the 5' u ntranslated region of the other three isoforms. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at