Genetic Variant DBH-AS1:n.1565C>G (chr9-133655160-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000425189.1(DBH-AS1):n.1565C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,202 control chromosomes in the GnomAD database, including 13,827 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 0.43 ( 13819 hom., cov: 33)

Exomes 𝑓: 0.51 ( 8 hom. )

Consequence

DBH-AS1
ENST00000425189.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.116

Publications

13 publications found

Variant links:

Genes affected

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

DBH-AS1 links:

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 Gene-Disease associations (from GenCC):

orthostatic hypotension 1
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

DBH links:

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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBH	NM_000787.4 link	c.1435-1363G>C		intron_variant	Intron 9 of 11	ENST00000393056.8	NP_000778.3
DBH-AS1	NR_102735.1 link	n.1660C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBH-AS1	ENST00000425189.1 link	n.1565C>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
DBH	ENST00000393056.8 link	c.1435-1363G>C		intron_variant	Intron 9 of 11	1	NM_000787.4	ENSP00000376776.2

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64648

AN:

152006

Hom.:

13805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.403

GnomAD4 exome

AF:

0.514

AC:

AN:

Hom.:

Cov.:

AF XY:

0.518

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.532

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.425

AC:

64692

AN:

152128

Hom.:

13819

Cov.:

AF XY:

0.422

AC XY:

31399

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.418

AC:

17332

AN:

41510

American (AMR)

AF:

0.430

AC:

6576

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1389

AN:

3470

East Asian (EAS)

AF:

0.524

AC:

2701

AN:

5158

South Asian (SAS)

AF:

0.335

AC:

1614

AN:

4824

European-Finnish (FIN)

AF:

0.429

AC:

4548

AN:

10592

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29018

AN:

67954

Other (OTH)

AF:

0.399

AC:

844

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1990

3980

5971

7961

9951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.268

Hom.:

617

Bravo

AF:

0.428

Asia WGS

AF:

0.417

AC:

1450

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

0.12

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