rs2007153

chr9-133638697-T-C

Variant summary

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

The NM_000787.4(DBH):c.340-1149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,034 control chromosomes in the GnomAD database, including 28,432 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 0.61 (28432 hom., cov: 32)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBH	NM_000787.4	c.340-1149T>C		intron_variant		ENST00000393056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBH	ENST00000393056.8	c.340-1149T>C		intron_variant		1	NM_000787.4	P1
DBH	ENST00000263611.3	c.333+1987T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92451 AN: 151916 Hom.: 28415 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.608 AC: 92511 AN: 152034 Hom.: 28432 Cov.: 32 AF XY: 0.613 AC XY: 45592 AN XY: 74330

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.605

Alfa AF: 0.611 Hom.: 56624

Bravo AF: 0.597

Asia WGS AF: 0.665 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.78
Dann	Benign	0.23

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: rs2007153; hg19: chr9-136503819;