rs129882

Variant names:

• chr9-133658547-C-T
• rs129882
• NM_000787.4:c.*100C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133658547-C-T
• chr9-133658547-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000787.4(DBH):​c.*100C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,336,366 control chromosomes in the GnomAD database, including 28,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3316 hom., cov: 32)
  • Exomes 𝑓: 0.20 (25465 hom.)
• Consequence: DBH NM_000787.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0780
• Publications: 27 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 Gene-Disease associations (from GenCC):

• orthostatic hypotension 1

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-133658547-C-T is Benign according to our data. Variant chr9-133658547-C-T is described in ClinVar as Benign. ClinVar VariationId is 365678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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.*100C>T		3_prime_UTR	Exon 12 of 12	NP_000778.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	ENST00000393056.8	TSL:1 MANE Select	c.*100C>T		3_prime_UTR	Exon 12 of 12	ENSP00000376776.2	P09172
	DBH	ENST00000860939.1		c.*100C>T		3_prime_UTR	Exon 12 of 12	ENSP00000530998.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30844 AN: 152080 Hom.: 3319 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.202 AC: 238629 AN: 1184168 Hom.: 25465 Cov.: 16 AF XY: 0.204 AC XY: 117499 AN XY: 576088

African (AFR) AF: 0.193 AC: 5037 AN: 26164

American (AMR) AF: 0.262 AC: 5247 AN: 20050

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 3571 AN: 18190

East Asian (EAS) AF: 0.390 AC: 12795 AN: 32798

South Asian (SAS) AF: 0.299 AC: 17036 AN: 56980

European-Finnish (FIN) AF: 0.156 AC: 6569 AN: 42158

Middle Eastern (MID) AF: 0.218 AC: 753 AN: 3458

European-Non Finnish (NFE) AF: 0.190 AC: 177144 AN: 934618

Other (OTH) AF: 0.211 AC: 10477 AN: 49752

GnomAD4 genome AF: 0.203 AC: 30860 AN: 152198 Hom.: 3316 Cov.: 32 AF XY: 0.205 AC XY: 15277 AN XY: 74434

African (AFR) AF: 0.199 AC: 8275 AN: 41534

American (AMR) AF: 0.226 AC: 3463 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1948 AN: 5158

South Asian (SAS) AF: 0.309 AC: 1490 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1586 AN: 10618

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12883 AN: 67986

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.192 Hom.: 4084

Bravo AF: 0.207

Asia WGS AF: 0.321 AC: 1118 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Orthostatic hypotension 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		-0.078
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: rs129882; hg19: chr9-136523669; COSMIC: COSV67549685; COSMIC: COSV67549685;