9-133646263-C-G

Position:

• chr9-133646263-C-G

Variant summary

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

The NM_000787.4(DBH):​c.1025-1583C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,852 control chromosomes in the GnomAD database, including 20,658 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 0.51 (20658 hom., cov: 31)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBH	NM_000787.4	c.1025-1583C>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.1025-1583C>G		intron_variant		1	NM_000787.4	ENSP00000376776.2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77402 AN: 151734 Hom.: 20635 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.0898

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.510 AC: 77493 AN: 151852 Hom.: 20658 Cov.: 31 AF XY: 0.497 AC XY: 36830 AN XY: 74166

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.0900

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.498

Alfa AF: 0.415 Hom.: 1151

Bravo AF: 0.509

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.61

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: rs1541333; hg19: chr9-136511385;