Variant 9-133639801-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.340-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 1,589,308 control chromosomes in the GnomAD database, including 3,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 178 hom., cov: 33)

Exomes 𝑓: 0.060 ( 2848 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.65

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:

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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=-0.87).

BP6

Variant 9-133639801-C-T is Benign according to our data. Variant chr9-133639801-C-T is described in ClinVar as [Benign]. Clinvar id is 1235638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 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.340-45C>T		intron_variant		ENST00000393056.8	NP_000778.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8 linkuse as main transcript	c.340-45C>T		intron_variant		1	NM_000787.4	ENSP00000376776	P1
DBH	ENST00000263611.3 linkuse as main transcript	c.334-2406C>T		intron_variant		2		ENSP00000263611

Frequencies

GnomAD3 genomes

AF:

0.0446

AC:

6791

AN:

152170

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0668

Gnomad EAS

AF:

0.0197

Gnomad SAS

AF:

0.0277

Gnomad FIN

AF:

0.0544

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0630

Gnomad OTH

AF:

0.0556

GnomAD3 exomes

AF:

0.0481

AC:

10346

AN:

215054

Hom.:

300

AF XY:

0.0485

AC XY:

5661

AN XY:

116760

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0724

Gnomad EAS exome

AF:

0.0222

Gnomad SAS exome

AF:

0.0333

Gnomad FIN exome

AF:

0.0551

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0597

AC:

85862

AN:

1437020

Hom.:

2848

Cov.:

AF XY:

0.0589

AC XY:

42012

AN XY:

713024

show subpopulations

Gnomad4 AFR exome

AF:

0.0153

Gnomad4 AMR exome

AF:

0.0288

Gnomad4 ASJ exome

AF:

0.0718

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.0574

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.0533

GnomAD4 genome

AF:

0.0446

AC:

6792

AN:

152288

Hom.:

178

Cov.:

AF XY:

0.0437

AC XY:

3256

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.0668

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0544

Gnomad4 NFE

AF:

0.0630

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0586

Hom.:

221

Bravo

AF:

0.0419

Asia WGS

AF:

0.0170

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 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.086

DANN

Benign

0.66

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