chr11-639273-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000797.4(DRD4):​c.286-160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DRD4 NM_000797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 12 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 512676 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 272474

African (AFR) AF: 0.00 AC: 0 AN: 14182

American (AMR) AF: 0.00 AC: 0 AN: 29338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16358

East Asian (EAS) AF: 0.00 AC: 0 AN: 29458

South Asian (SAS) AF: 0.00 AC: 0 AN: 56582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 306874

Other (OTH) AF: 0.00 AC: 0 AN: 27648

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 2210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.95
PhyloP100		-2.4
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

Other links and lift over

dbSNP: rs7124601; hg19: chr11-639273;