rs2097628

Positions:

• chr9-133654580-A-G
• chr9-133654580-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000787.4(DBH):​c.1434+1581A>G 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 151,782 control chromosomes in the GnomAD database, including 11,828 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 0.39 (11825 hom., cov: 33)
  • Exomes 𝑓: 0.60 (3 hom.)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBH	NM_000787.4	c.1434+1581A>G		intron_variant		ENST00000393056.8	NP_000778.3
DBH-AS1	NR_102735.1	n.*7T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.1434+1581A>G		intron_variant		1	NM_000787.4	ENSP00000376776.2
DBH-AS1	ENST00000425189.1	n.*6T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59738 AN: 151644 Hom.: 11812 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.600 AC: 12 AN: 20 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 8 AN XY: 12

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.643

GnomAD4 genome AF: 0.394 AC: 59787 AN: 151762 Hom.: 11825 Cov.: 33 AF XY: 0.391 AC XY: 29035 AN XY: 74164

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.370

Alfa AF: 0.376 Hom.: 16341

Bravo AF: 0.403

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.43

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: rs2097628; hg19: chr9-136519702;