Variant rs1108581 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.486+127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,295,830 control chromosomes in the GnomAD database, including 30,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6092 hom., cov: 33)

Exomes 𝑓: 0.20 ( 24027 hom. )

Consequence

DBH
NM_000787.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.193

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=-0.92).

BP6

Variant 9-133640119-A-G is Benign according to our data. Variant chr9-133640119-A-G is described in ClinVar as [Benign]. Clinvar id is 1258192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 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.486+127A>G		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.486+127A>G		intron_variant		1	NM_000787.4	ENSP00000376776	P1
DBH	ENST00000263611.3 linkuse as main transcript	c.334-2088A>G		intron_variant		2		ENSP00000263611

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39432

AN:

152086

Hom.:

6069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.198

AC:

226223

AN:

1143626

Hom.:

24027

AF XY:

0.197

AC XY:

113094

AN XY:

575106

show subpopulations

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.260

AC:

39502

AN:

152204

Hom.:

6092

Cov.:

AF XY:

0.254

AC XY:

18871

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.211

Hom.:

4845

Bravo

AF:

0.266

Asia WGS

AF:

0.195

AC:

680

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	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.6

DANN

Benign

0.68

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