9-133655160-G-C

Position:

• chr9-133655160-G-C

Variant summary

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

The ENST00000393056.8(DBH):​c.1435-1363G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,202 control chromosomes in the GnomAD database, including 13,827 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 0.43 (13819 hom., cov: 33)
  • Exomes 𝑓: 0.51 (8 hom.)
• Consequence: DBH ENST00000393056.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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-AS1 (HGNC:24155): (DBH antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBH	NM_000787.4	c.1435-1363G>C		intron_variant		ENST00000393056.8	NP_000778.3
DBH-AS1	NR_102735.1	n.1660C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBH	ENST00000393056.8	c.1435-1363G>C		intron_variant		1	NM_000787.4	ENSP00000376776	P1
DBH-AS1	ENST00000425189.1	n.1565C>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64648 AN: 152006 Hom.: 13805 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.514 AC: 38 AN: 74 Hom.: 8 Cov.: 0 AF XY: 0.518 AC XY: 29 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.425 AC: 64692 AN: 152128 Hom.: 13819 Cov.: 33 AF XY: 0.422 AC XY: 31399 AN XY: 74382

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.399

Alfa AF: 0.268 Hom.: 617

Bravo AF: 0.428

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.51

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: rs2073833; hg19: chr9-136520282;