Variant 9-133656475-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000787.4(DBH):c.1435-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,612,330 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 209 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 203 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.58

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-133656475-C-T is Benign according to our data. Variant chr9-133656475-C-T is described in ClinVar as [Benign]. Clinvar id is 1269946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBH	NM_000787.4 linkuse as main transcript	c.1435-48C>T		intron_variant		ENST00000393056.8	NP_000778.3
DBH-AS1	NR_102735.1 linkuse as main transcript	n.345G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8 linkuse as main transcript	c.1435-48C>T		intron_variant		1	NM_000787.4	ENSP00000376776	P1
DBH-AS1	ENST00000425189.1 linkuse as main transcript	n.250G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4534

AN:

152142

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.00930

AC:

2316

AN:

249058

Hom.:

AF XY:

0.00768

AC XY:

1037

AN XY:

134996

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00559

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00624

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000872

Gnomad OTH exome

AF:

0.00675

GnomAD4 exome

AF:

0.00396

AC:

5784

AN:

1460070

Hom.:

203

Cov.:

AF XY:

0.00368

AC XY:

2670

AN XY:

726350

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00608

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000467

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.0299

AC:

4551

AN:

152260

Hom.:

209

Cov.:

AF XY:

0.0290

AC XY:

2160

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00644

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0183

Hom.:

Bravo

AF:

0.0329

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.20

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over