9-133640522-T-C

Variant names:

• chr9-133640522-T-C
• rs2873804
• NM_000787.4:c.486+530T>C

Variant summary

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

The NM_000787.4(DBH):​c.486+530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,116 control chromosomes in the GnomAD database, including 21,889 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 0.52 (21889 hom., cov: 33)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DBH	NM_000787.4	c.486+530T>C		intron_variant	Intron 2 of 11	ENST00000393056.8	NP_000778.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.486+530T>C		intron_variant	Intron 2 of 11	1	NM_000787.4	ENSP00000376776.2
DBH	ENST00000263611.3	c.334-1685T>C		intron_variant	Intron 1 of 2	2		ENSP00000263611.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79523 AN: 151998 Hom.: 21851 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.523 AC: 79627 AN: 152116 Hom.: 21889 Cov.: 33 AF XY: 0.512 AC XY: 38063 AN XY: 74384

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.502

Alfa AF: 0.514 Hom.: 33024

Bravo AF: 0.521

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.54

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: rs2873804; hg19: chr9-136505644;