Variant 11-637294-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0620

Variant links:

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]

DRD4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD4	NM_000797.4 linkuse as main transcript	c.-11C>T		5_prime_UTR_variant	1/4	ENST00000176183.6	NP_000788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD4	ENST00000176183.6 linkuse as main transcript	c.-11C>T		5_prime_UTR_variant	1/4	1	NM_000797.4	ENSP00000176183	P1

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6396

AN:

150986

Hom.:

158

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0515

AC:

319

AN:

6198

Hom.:

AF XY:

0.0503

AC XY:

201

AN XY:

3994

show subpopulations

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 SAS exome

AF:

0.0608

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.:

AF XY:

0.0533

AC XY:

26405

AN XY:

495470

show subpopulations

Gnomad4 AFR exome

AF:

0.0186

Gnomad4 AMR exome

AF:

0.0468

Gnomad4 ASJ exome

AF:

0.0794

Gnomad4 EAS exome

AF:

0.000190

Gnomad4 SAS exome

AF:

0.0801

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0542

Gnomad4 OTH exome

AF:

0.0574

GnomAD4 genome

AF:

0.0424

AC:

6404

AN:

151094

Hom.:

157

Cov.:

AF XY:

0.0426

AC XY:

3146

AN XY:

73860

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.0721

Gnomad4 FIN

AF:

0.0362

Gnomad4 NFE

AF:

0.0537

Gnomad4 OTH

AF:

0.0523

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0428

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary attention deficit-hyperactivity disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Potent mutations in Dopamine receptor uptake gene leads to decreased brain uptake of neuromodulator dopamine and are strongly associated with onset of Attention deficit hyperactivity disorder. However more evidence is required to confer the association of this particular rs146680769 with Attention deficit hyperactivity disorder. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.3

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over