Variant 9-133644190-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.922-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,564,790 control chromosomes in the GnomAD database, including 206,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20354 hom., cov: 33)

Exomes 𝑓: 0.50 ( 186063 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.939

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=-0.98).

BP6

Variant 9-133644190-C-T is Benign according to our data. Variant chr9-133644190-C-T is described in ClinVar as [Benign]. Clinvar id is 1246402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 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.922-28C>T		intron_variant		ENST00000393056.8	NP_000778.3	P09172

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8 linkuse as main transcript	c.922-28C>T		intron_variant		1	NM_000787.4	ENSP00000376776.2		P09172

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

77092

AN:

151996

Hom.:

20317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.485

GnomAD3 exomes

AF:

0.438

AC:

109897

AN:

250822

Hom.:

26678

AF XY:

0.439

AC XY:

59497

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.532

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.503

AC:

710862

AN:

1412676

Hom.:

186063

Cov.:

AF XY:

0.497

AC XY:

351000

AN XY:

705888

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.540

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.507

AC:

77191

AN:

152114

Hom.:

20354

Cov.:

AF XY:

0.497

AC XY:

36949

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.596

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.483

Gnomad4 NFE

AF:

0.534

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.522

Hom.:

4692

Bravo

AF:

0.503

Asia WGS

AF:

0.262

AC:

913

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 11, 2021	- -

Orthostatic hypotension 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.22

DANN

Benign

0.41

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

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