rs6271
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000787.4(DBH):c.1645C>T(p.Arg549Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,614,048 control chromosomes in the GnomAD database, including 3,557 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R549H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000787.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DBH | NM_000787.4 | c.1645C>T | p.Arg549Cys | missense_variant | 11/12 | ENST00000393056.8 | |
DBH-AS1 | NR_102735.1 | n.257G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DBH | ENST00000393056.8 | c.1645C>T | p.Arg549Cys | missense_variant | 11/12 | 1 | NM_000787.4 | P1 | |
DBH-AS1 | ENST00000425189.1 | n.162G>A | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0475 AC: 7231AN: 152160Hom.: 239 Cov.: 32
GnomAD3 exomes AF: 0.0461 AC: 11580AN: 251400Hom.: 357 AF XY: 0.0460 AC XY: 6258AN XY: 135896
GnomAD4 exome AF: 0.0629 AC: 92009AN: 1461770Hom.: 3318 Cov.: 35 AF XY: 0.0615 AC XY: 44710AN XY: 727184
GnomAD4 genome ? AF: 0.0475 AC: 7229AN: 152278Hom.: 239 Cov.: 32 AF XY: 0.0466 AC XY: 3467AN XY: 74456
ClinVar
Submissions by phenotype
Orthostatic hypotension 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 22, 2019 | This variant is associated with the following publications: (PMID: 21085059, 30817802, 16152569, 22028891, 21509519) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at