11-637335-G-T

Variant names:

• chr11-637335-G-T
• rs189482961
• NM_000797.4:c.31G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_000797.4(DRD4):​c.31G>T​(p.Gly11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,112,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G11R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: DRD4 NM_000797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 6 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30253807).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000797.4. 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
	DRD4	NM_000797.4	MANE Select	c.31G>T	p.Gly11Trp	missense	Exon 1 of 4	NP_000788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	ENST00000176183.6	TSL:1 MANE Select	c.31G>T	p.Gly11Trp	missense	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000629 AC: 7 AN: 1112418 Hom.: 0 Cov.: 31 AF XY: 0.00000751 AC XY: 4 AN XY: 532384

African (AFR) AF: 0.000225 AC: 5 AN: 22236

American (AMR) AF: 0.00 AC: 0 AN: 8026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14088

East Asian (EAS) AF: 0.00 AC: 0 AN: 24680

South Asian (SAS) AF: 0.00 AC: 0 AN: 30002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 942162

Other (OTH) AF: 0.0000448 AC: 2 AN: 44648

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.6
DANN	Benign	0.65
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.022	N
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.92	T
PhyloP100		-1.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.099
Sift	Benign	0.058	T
Sift4G	Pathogenic	0.0	D
Vest4		0.25
MutPred		0.35		Loss of disorder (P = 0.0132)
MVP		0.67
MPC		0.33
ClinPred		0.79	D
GERP RS		-2.9
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.58
Mutation Taster		=98/2	polymorphism

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: rs189482961; hg19: chr11-637335;