rs2797849

Variant names:

• chr9-133636819-G-C
• rs2797849
• NM_000787.4:c.339+109G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133636819-G-C
• chr9-133636819-G-A
• chr9-133636819-G-T

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.339+109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,042,436 control chromosomes in the GnomAD database, including 51,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7746 hom., cov: 32)
  • Exomes 𝑓: 0.30 (44136 hom.)
• Consequence: DBH NM_000787.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0930
• Publications: 13 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=-0.91).
• BP6: Variant 9-133636819-G-C is Benign according to our data. Variant chr9-133636819-G-C is described in ClinVar as Benign. ClinVar VariationId is 1282926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 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.339+109G>C		intron	N/A	NP_000778.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBH	ENST00000393056.8	TSL:1 MANE Select	c.339+109G>C		intron	N/A	ENSP00000376776.2	P09172
	DBH	ENST00000860939.1		c.339+109G>C		intron	N/A	ENSP00000530998.1
	DBH	ENST00000263611.3	TSL:2	c.333+109G>C		intron	N/A	ENSP00000263611.3	Q5T382

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47110 AN: 151796 Hom.: 7738 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.299 AC: 265836 AN: 890522 Hom.: 44136 AF XY: 0.294 AC XY: 134579 AN XY: 458442

African (AFR) AF: 0.331 AC: 7354 AN: 22212

American (AMR) AF: 0.193 AC: 6807 AN: 35186

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 5473 AN: 22122

East Asian (EAS) AF: 0.00160 AC: 54 AN: 33652

South Asian (SAS) AF: 0.141 AC: 9739 AN: 69314

European-Finnish (FIN) AF: 0.342 AC: 11538 AN: 33746

Middle Eastern (MID) AF: 0.242 AC: 1103 AN: 4564

European-Non Finnish (NFE) AF: 0.338 AC: 212027 AN: 627836

Other (OTH) AF: 0.280 AC: 11741 AN: 41890

GnomAD4 genome AF: 0.310 AC: 47146 AN: 151914 Hom.: 7746 Cov.: 32 AF XY: 0.304 AC XY: 22541 AN XY: 74254

African (AFR) AF: 0.340 AC: 14080 AN: 41386

American (AMR) AF: 0.246 AC: 3754 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5170

South Asian (SAS) AF: 0.131 AC: 632 AN: 4816

European-Finnish (FIN) AF: 0.334 AC: 3519 AN: 10538

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23367 AN: 67954

Other (OTH) AF: 0.290 AC: 611 AN: 2104

Alfa AF: 0.196 Hom.: 433

Bravo AF: 0.304

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.49
PhyloP100		-0.093
PromoterAI		0.029	Neutral
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: rs2797849; hg19: chr9-136501941;