11-637560-C-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000797.4(DRD4):c.256C>A(p.Leu86Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000475 in 1,558,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
DRD4
NM_000797.4 missense
NM_000797.4 missense
Scores
1
9
6
Clinical Significance
Conservation
PhyloP100: 5.26
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRD4 | NM_000797.4 | c.256C>A | p.Leu86Met | missense_variant | 1/4 | ENST00000176183.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRD4 | ENST00000176183.6 | c.256C>A | p.Leu86Met | missense_variant | 1/4 | 1 | NM_000797.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000244 AC: 4AN: 164114Hom.: 0 AF XY: 0.0000339 AC XY: 3AN XY: 88604
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GnomAD4 exome AF: 0.0000455 AC: 64AN: 1406428Hom.: 0 Cov.: 32 AF XY: 0.0000431 AC XY: 30AN XY: 695698
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.256C>A (p.L86M) alteration is located in exon 1 (coding exon 1) of the DRD4 gene. This alteration results from a C to A substitution at nucleotide position 256, causing the leucine (L) at amino acid position 86 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at