NM_000797.4:c.-11C>T

Variant names:

• chr11-637294-C-T
• rs146680769
• NM_000797.4:c.-11C>T

Variant summary

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

The NM_000797.4(DRD4):​c.-11C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,196,094 control chromosomes in the GnomAD database, including 1,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.042 (157 hom., cov: 32)
  • Exomes 𝑓: 0.053 (1600 hom.)
• Consequence: DRD4 NM_000797.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

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.-11C>T		5_prime_UTR	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.-11C>T		5_prime_UTR	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6396 AN: 150986 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0905

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0524

GnomAD2 exomes AF: 0.0515 AC: 319 AN: 6198 AF XY: 0.0503

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0210

Gnomad ASJ exome AF: 0.0811

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0520

Gnomad OTH exome AF: 0.0333

GnomAD4 exome AF: 0.0530 AC: 55428 AN: 1045000 Hom.: 1600 Cov.: 30 AF XY: 0.0533 AC XY: 26405 AN XY: 495470

African (AFR) AF: 0.0186 AC: 391 AN: 21018

American (AMR) AF: 0.0468 AC: 342 AN: 7310

Ashkenazi Jewish (ASJ) AF: 0.0794 AC: 981 AN: 12362

East Asian (EAS) AF: 0.000190 AC: 4 AN: 21048

South Asian (SAS) AF: 0.0801 AC: 1816 AN: 22662

European-Finnish (FIN) AF: 0.0379 AC: 751 AN: 19796

Middle Eastern (MID) AF: 0.0681 AC: 186 AN: 2730

European-Non Finnish (NFE) AF: 0.0542 AC: 48637 AN: 897660

Other (OTH) AF: 0.0574 AC: 2320 AN: 40414

GnomAD4 genome AF: 0.0424 AC: 6404 AN: 151094 Hom.: 157 Cov.: 32 AF XY: 0.0426 AC XY: 3146 AN XY: 73860

African (AFR) AF: 0.0218 AC: 900 AN: 41354

American (AMR) AF: 0.0450 AC: 684 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 271 AN: 3458

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5094

South Asian (SAS) AF: 0.0721 AC: 347 AN: 4812

European-Finnish (FIN) AF: 0.0362 AC: 372 AN: 10280

Middle Eastern (MID) AF: 0.0313 AC: 9 AN: 288

European-Non Finnish (NFE) AF: 0.0537 AC: 3628 AN: 67614

Other (OTH) AF: 0.0523 AC: 110 AN: 2102

Alfa AF: 0.0201 Hom.: 9

Bravo AF: 0.0428

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary attention deficit-hyperactivity disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.97
PhyloP100		0.062
PromoterAI		-0.020	Neutral
Mutation Taster		=300/0	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: rs146680769; hg19: chr11-637294;