rs2519152

chr9-133644512-T-C

Variant summary

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

The NM_000787.4(DBH):c.1024+192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,128 control chromosomes in the GnomAD database, including 12,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (12366 hom., cov: 33)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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=-0.94).
• BP6: Variant 9-133644512-T-C is Benign according to our data. Variant chr9-133644512-T-C is described in ClinVar as [Benign]. Clinvar id is 1240982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBH	NM_000787.4	c.1024+192T>C		intron_variant		ENST00000393056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBH	ENST00000393056.8	c.1024+192T>C		intron_variant		1	NM_000787.4	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59952 AN: 152010 Hom.: 12357 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.394 AC: 60006 AN: 152128 Hom.: 12366 Cov.: 33 AF XY: 0.387 AC XY: 28756 AN XY: 74384

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.386

Alfa AF: 0.441 Hom.: 2292

Bravo AF: 0.385

Asia WGS AF: 0.230 AC: 798 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	-0.94
Cadd	Benign	0.37
Dann	Benign	0.62

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: rs2519152; hg19: chr9-136509634;