11-639273-C-A

Variant names:

• chr11-639273-C-A
• rs7124601
• NM_000797.4:c.286-160C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000797.4(DRD4):​c.286-160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 663,228 control chromosomes in the GnomAD database, including 69,681 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 0.47 (17029 hom., cov: 30)
  • Exomes 𝑓: 0.45 (52652 hom.)
• Consequence: DRD4 NM_000797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD4	NM_000797.4	c.286-160C>A		intron_variant	Intron 1 of 3	ENST00000176183.6	NP_000788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD4	ENST00000176183.6	c.286-160C>A		intron_variant	Intron 1 of 3	1	NM_000797.4	ENSP00000176183.5
DRD4	ENST00000528733.1	n.102+115C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71254 AN: 151562 Hom.: 17019 Cov.: 30

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.447 AC: 228645 AN: 511546 Hom.: 52652 Cov.: 6 AF XY: 0.446 AC XY: 121282 AN XY: 271892

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.470 AC: 71294 AN: 151682 Hom.: 17029 Cov.: 30 AF XY: 0.465 AC XY: 34453 AN XY: 74112

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.486

Alfa AF: 0.413 Hom.: 2210

Bravo AF: 0.475

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.91
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs7124601; hg19: chr11-639273;