rs1548364

Positions:

• chr9-133642620-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000393056.8(DBH):​c.744+156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,874 control chromosomes in the GnomAD database, including 22,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (22102 hom., cov: 31)
• Consequence: DBH ENST00000393056.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-133642620-A-G is Benign according to our data. Variant chr9-133642620-A-G is described in ClinVar as [Benign]. Clinvar id is 1257835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBH	NM_000787.4	c.744+156A>G		intron_variant		ENST00000393056.8	NP_000778.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.744+156A>G		intron_variant		1	NM_000787.4	ENSP00000376776	P1
DBH	ENST00000263611.3	c.591+156A>G		intron_variant		2		ENSP00000263611

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80001 AN: 151756 Hom.: 22063 Cov.: 31

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.527 AC: 80104 AN: 151874 Hom.: 22102 Cov.: 31 AF XY: 0.517 AC XY: 38362 AN XY: 74210

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.504

Alfa AF: 0.539 Hom.: 2780

Bravo AF: 0.523

Asia WGS AF: 0.300 AC: 1047 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.039
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs1548364; hg19: chr9-136507742;