rs2007153

Variant names:

• chr9-133638697-T-C
• rs2007153
• NM_000787.4:c.340-1149T>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.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
• Publications: 21 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=-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 rank	MANE	Protein	UniProt
DBH	NM_000787.4	c.340-1149T>C		intron_variant	Intron 1 of 11	ENST00000393056.8	NP_000778.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.340-1149T>C		intron_variant	Intron 1 of 11	1	NM_000787.4	ENSP00000376776.2
DBH	ENST00000263611.3	c.333+1987T>C		intron_variant	Intron 1 of 2	2		ENSP00000263611.3

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

African (AFR) AF: 0.542 AC: 22479 AN: 41440

American (AMR) AF: 0.597 AC: 9118 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3561 AN: 5152

South Asian (SAS) AF: 0.632 AC: 3045 AN: 4816

European-Finnish (FIN) AF: 0.722 AC: 7659 AN: 10606

Middle Eastern (MID) AF: 0.603 AC: 175 AN: 290

European-Non Finnish (NFE) AF: 0.627 AC: 42613 AN: 67958

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.612 Hom.: 122430

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
PhyloP100		-3.4
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: rs2007153; hg19: chr9-136503819;