chr9-133654578-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000787.4(DBH):​c.1434+1579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,808 control chromosomes in the GnomAD database, including 11,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11702 hom., cov: 33)
Exomes 𝑓: 0.55 ( 3 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

Publications

6 publications found
Variant links:
Genes affected
DBH (HGNC:2689): (dopamine beta-hydroxylase) The protein encoded by this gene is an oxidoreductase belonging to the copper type II, ascorbate-dependent monooxygenase family. The encoded protein, expressed in neuroscretory vesicles and chromaffin granules of the adrenal medulla, catalyzes the conversion of dopamine to norepinephrine, which functions as both a hormone and as the main neurotransmitter of the sympathetic nervous system. The enzyme encoded by this gene exists exists in both soluble and membrane-bound forms, depending on the absence or presence, respectively, of a signal peptide. Mutations in this gene cause dopamine beta-hydroxylate deficiency in human patients, characterized by deficits in autonomic and cardiovascular function, including hypotension and ptosis. Polymorphisms in this gene may play a role in a variety of psychiatric disorders. [provided by RefSeq, Aug 2017]
DBH-AS1 (HGNC:24155): (DBH antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DBHNM_000787.4 linkc.1434+1579A>G intron_variant Intron 9 of 11 ENST00000393056.8 NP_000778.3 P09172
DBH-AS1NR_102735.1 linkn.*9T>C downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DBHENST00000393056.8 linkc.1434+1579A>G intron_variant Intron 9 of 11 1 NM_000787.4 ENSP00000376776.2 P09172
DBH-AS1ENST00000425189.1 linkn.*8T>C downstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.392
AC:
59443
AN:
151670
Hom.:
11689
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.423
Gnomad AMI
AF:
0.569
Gnomad AMR
AF:
0.402
Gnomad ASJ
AF:
0.369
Gnomad EAS
AF:
0.514
Gnomad SAS
AF:
0.312
Gnomad FIN
AF:
0.363
Gnomad MID
AF:
0.395
Gnomad NFE
AF:
0.371
Gnomad OTH
AF:
0.372
GnomAD4 exome
AF:
0.545
AC:
12
AN:
22
Hom.:
3
Cov.:
0
AF XY:
0.571
AC XY:
8
AN XY:
14
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AF:
0.500
AC:
1
AN:
2
European-Finnish (FIN)
AF:
0.333
AC:
2
AN:
6
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.643
AC:
9
AN:
14
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.392
AC:
59492
AN:
151786
Hom.:
11702
Cov.:
33
AF XY:
0.389
AC XY:
28885
AN XY:
74180
show subpopulations
African (AFR)
AF:
0.423
AC:
17513
AN:
41372
American (AMR)
AF:
0.402
AC:
6124
AN:
15252
Ashkenazi Jewish (ASJ)
AF:
0.369
AC:
1274
AN:
3452
East Asian (EAS)
AF:
0.514
AC:
2650
AN:
5154
South Asian (SAS)
AF:
0.313
AC:
1508
AN:
4822
European-Finnish (FIN)
AF:
0.363
AC:
3831
AN:
10542
Middle Eastern (MID)
AF:
0.397
AC:
116
AN:
292
European-Non Finnish (NFE)
AF:
0.371
AC:
25180
AN:
67878
Other (OTH)
AF:
0.368
AC:
779
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1872
3743
5615
7486
9358
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
560
1120
1680
2240
2800
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.384
Hom.:
1457
Bravo
AF:
0.401
Asia WGS
AF:
0.398
AC:
1384
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
4.3
DANN
Benign
0.66
PhyloP100
0.50
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2097629; hg19: chr9-136519700; API