rs732833

Variant names:

• chr9-133655540-T-C
• rs732833
• NM_000787.4:c.1435-983T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133655540-T-C
• chr9-133655540-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000787.4(DBH):​c.1435-983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,196 control chromosomes in the GnomAD database, including 13,611 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 0.42 (13599 hom., cov: 33)
  • Exomes 𝑓: 0.44 (12 hom.)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 8 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-AS1 (HGNC:24155): (DBH antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000787.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	NM_000787.4	MANE Select	c.1435-983T>C		intron	N/A	NP_000778.3
	DBH-AS1	NR_102735.1		n.1280A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	ENST00000393056.8	TSL:1 MANE Select	c.1435-983T>C		intron	N/A	ENSP00000376776.2	P09172
	DBH-AS1	ENST00000425189.1	TSL:1	n.1185A>G		non_coding_transcript_exon	Exon 2 of 2
	DBH	ENST00000860939.1		c.1435-983T>C		intron	N/A	ENSP00000530998.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64089 AN: 151976 Hom.: 13583 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.441 AC: 45 AN: 102 Hom.: 12 Cov.: 0 AF XY: 0.443 AC XY: 31 AN XY: 70

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 30 AN: 80

Other (OTH) AF: 0.700 AC: 7 AN: 10

GnomAD4 genome AF: 0.422 AC: 64134 AN: 152094 Hom.: 13599 Cov.: 33 AF XY: 0.419 AC XY: 31157 AN XY: 74366

African (AFR) AF: 0.399 AC: 16564 AN: 41482

American (AMR) AF: 0.431 AC: 6588 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2719 AN: 5162

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4828

European-Finnish (FIN) AF: 0.430 AC: 4545 AN: 10580

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29187 AN: 67970

Other (OTH) AF: 0.399 AC: 843 AN: 2114

Alfa AF: 0.422 Hom.: 5708

Bravo AF: 0.425

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.45
PhyloP100		-4.3
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: rs732833; hg19: chr9-136520662; COSMIC: COSV67548955;