3-114160557-G-A

Variant names:

• chr3-114160557-G-A
• rs11721264
• NM_000796.6:c.271-690C>T

Variant summary

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

The NM_000796.6(DRD3):​c.271-690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,128 control chromosomes in the GnomAD database, including 13,097 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 (13097 hom., cov: 32)
• Consequence: DRD3 NM_000796.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 12 publications found

Genes affected

DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD3	NM_000796.6	c.271-690C>T		intron_variant	Intron 2 of 6	ENST00000383673.5	NP_000787.2
DRD3	NM_001282563.2	c.271-690C>T		intron_variant	Intron 3 of 7		NP_001269492.1
DRD3	NM_001290809.1	c.271-690C>T		intron_variant	Intron 3 of 7		NP_001277738.1
DRD3	NM_033663.6	c.271-690C>T		intron_variant	Intron 2 of 7		NP_387512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000383673.5	c.271-690C>T		intron_variant	Intron 2 of 6	1	NM_000796.6	ENSP00000373169.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58801 AN: 152010 Hom.: 13077 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.387 AC: 58871 AN: 152128 Hom.: 13097 Cov.: 32 AF XY: 0.388 AC XY: 28870 AN XY: 74370

African (AFR) AF: 0.613 AC: 25405 AN: 41472

American (AMR) AF: 0.396 AC: 6050 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1422 AN: 5180

South Asian (SAS) AF: 0.337 AC: 1628 AN: 4824

European-Finnish (FIN) AF: 0.306 AC: 3237 AN: 10588

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19024 AN: 67986

Other (OTH) AF: 0.365 AC: 770 AN: 2110

Alfa AF: 0.178 Hom.: 388

Bravo AF: 0.402

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.65
PhyloP100		1.4
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: rs11721264; hg19: chr3-113879404;