rs2073837

Variant names:

• chr9-133657806-G-A
• rs2073837
• NM_000787.4:c.1723-510G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133657806-G-A
• chr9-133657806-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000787.4(DBH):​c.1723-510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,092 control chromosomes in the GnomAD database, including 7,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7644 hom., cov: 32)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• orthostatic hypotension 1

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBH	NM_000787.4	c.1723-510G>A		intron_variant	Intron 11 of 11	ENST00000393056.8	NP_000778.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.1723-510G>A		intron_variant	Intron 11 of 11	1	NM_000787.4	ENSP00000376776.2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47303 AN: 151974 Hom.: 7634 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.311 AC: 47338 AN: 152092 Hom.: 7644 Cov.: 32 AF XY: 0.315 AC XY: 23438 AN XY: 74328

African (AFR) AF: 0.247 AC: 10244 AN: 41496

American (AMR) AF: 0.388 AC: 5935 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1262 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2395 AN: 5154

South Asian (SAS) AF: 0.307 AC: 1475 AN: 4810

European-Finnish (FIN) AF: 0.388 AC: 4104 AN: 10576

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20742 AN: 67976

Other (OTH) AF: 0.330 AC: 699 AN: 2116

Alfa AF: 0.190 Hom.: 408

Bravo AF: 0.310

Asia WGS AF: 0.405 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.59
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2073837; hg19: chr9-136522928; COSMIC: COSV67548962; COSMIC: COSV67548962;