dbSNP rs2097628: DBH:c.1434+1581A>G (chr9-133654580-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000787.4(DBH):c.1434+1581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,782 control chromosomes in the GnomAD database, including 11,828 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 ( 11825 hom., cov: 33)

Exomes 𝑓: 0.60 ( 3 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.993

Publications

15 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 links:

DBH-AS1 (HGNC:24155): (DBH antisense RNA 1)

DBH-AS1 links:

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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=-1.03).

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
DBH	NM_000787.4 link	c.1434+1581A>G		intron_variant	Intron 9 of 11	ENST00000393056.8	NP_000778.3	P09172
DBH-AS1	NR_102735.1 link	n.*7T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8 link	c.1434+1581A>G		intron_variant	Intron 9 of 11	1	NM_000787.4	ENSP00000376776.2		P09172
DBH-AS1	ENST00000425189.1 link	n.*6T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59738

AN:

151644

Hom.:

11812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.398

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.374

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.643

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.394

AC:

59787

AN:

151762

Hom.:

11825

Cov.:

AF XY:

0.391

AC XY:

29035

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.425

AC:

17566

AN:

41362

American (AMR)

AF:

0.405

AC:

6186

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1274

AN:

3454

East Asian (EAS)

AF:

0.515

AC:

2651

AN:

5152

South Asian (SAS)

AF:

0.314

AC:

1511

AN:

4812

European-Finnish (FIN)

AF:

0.364

AC:

3836

AN:

10534

Middle Eastern (MID)

AF:

0.401

AC:

117

AN:

292

European-Non Finnish (NFE)

AF:

0.373

AC:

25341

AN:

67876

Other (OTH)

AF:

0.370

AC:

782

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1887

3774

5662

7549

9436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.378

Hom.:

27565

Bravo

AF:

0.403

Asia WGS

AF:

0.398

AC:

1385

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

0.32

(source)

DANN

Benign

0.43

PhyloP100

-0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over