rs3025388

chr9-133638134-A-Gchr9-133638134-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.339+1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,264 control chromosomes in the GnomAD database, including 4,250 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 0.22 (4250 hom., cov: 34)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBH	NM_000787.4	c.339+1424A>G		intron_variant		ENST00000393056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBH	ENST00000393056.8	c.339+1424A>G		intron_variant		1	NM_000787.4	P1
DBH	ENST00000263611.3	c.333+1424A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32813 AN: 152146 Hom.: 4238 Cov.: 34

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.216 AC: 32860 AN: 152264 Hom.: 4250 Cov.: 34 AF XY: 0.212 AC XY: 15752 AN XY: 74466

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.196

Alfa AF: 0.167 Hom.: 2131

Bravo AF: 0.222

Asia WGS AF: 0.155 AC: 541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.026
Dann	Benign	0.26

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: rs3025388; hg19: chr9-136503256;