rs2097629

Variant names:

• chr9-133654578-A-G
• rs2097629
• NM_000787.4:c.1434+1579A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-133654578-A-G
• chr9-133654578-A-T

Variant summary

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

The NM_000787.4(DBH):​c.1434+1579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,808 control chromosomes in the GnomAD database, including 11,705 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 0.39 (11702 hom., cov: 33)
  • Exomes 𝑓: 0.55 (3 hom.)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	NM_000787.4	MANE Select	c.1434+1579A>G		intron	N/A	NP_000778.3
	DBH-AS1	NR_102735.1		n.*9T>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	ENST00000393056.8	TSL:1 MANE Select	c.1434+1579A>G		intron	N/A	ENSP00000376776.2
	DBH-AS1	ENST00000425189.1	TSL:1	n.*8T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59443 AN: 151670 Hom.: 11689 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.545 AC: 12 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.571 AC XY: 8 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.643 AC: 9 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.392 AC: 59492 AN: 151786 Hom.: 11702 Cov.: 33 AF XY: 0.389 AC XY: 28885 AN XY: 74180

African (AFR) AF: 0.423 AC: 17513 AN: 41372

American (AMR) AF: 0.402 AC: 6124 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1274 AN: 3452

East Asian (EAS) AF: 0.514 AC: 2650 AN: 5154

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3831 AN: 10542

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25180 AN: 67878

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.384 Hom.: 1457

Bravo AF: 0.401

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.66
PhyloP100		0.50
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: rs2097629; hg19: chr9-136519700;