dbSNP rs1470750: DDC:c.715-4891G>C (chr7-50508950-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001082971.2(DDC):c.715-4891G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,104 control chromosomes in the GnomAD database, including 8,190 homozygotes. 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: 𝑓 0.30 ( 8190 hom., cov: 32)

Consequence

DDC
NM_001082971.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

17 publications found

Variant links:

Genes affected

DDC (HGNC:2719): (dopa decarboxylase) The encoded protein catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in this gene are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2011]

DDC Gene-Disease associations (from GenCC):

aromatic L-amino acid decarboxylase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

DDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDC	NM_001082971.2	MANE Select	c.715-4891G>C	intron	N/A	NP_001076440.2	A0A0S2Z3N4
DDC	NM_000790.4		c.715-4891G>C	intron	N/A	NP_000781.2	P20711-1
DDC	NM_001242886.2		c.601-4891G>C	intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDC	ENST00000444124.7	TSL:1 MANE Select	c.715-4891G>C	intron	N/A	ENSP00000403644.2	P20711-1
DDC	ENST00000357936.9	TSL:1	c.715-4891G>C	intron	N/A	ENSP00000350616.5	P20711-1
DDC	ENST00000380984.4	TSL:1	c.715-4891G>C	intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44966

AN:

151986

Hom.:

8185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.296

AC:

44969

AN:

152104

Hom.:

8190

Cov.:

AF XY:

0.289

AC XY:

21487

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0766

AC:

3183

AN:

41538

American (AMR)

AF:

0.350

AC:

5350

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1533

AN:

3470

East Asian (EAS)

AF:

0.244

AC:

1259

AN:

5168

South Asian (SAS)

AF:

0.247

AC:

1188

AN:

4812

European-Finnish (FIN)

AF:

0.307

AC:

3244

AN:

10566

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27931

AN:

67962

Other (OTH)

AF:

0.343

AC:

725

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1494

2989

4483

5978

7472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.336

Hom.:

1174

Bravo

AF:

0.293

Asia WGS

AF:

0.262

AC:

914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.91

(source)

DANN

Benign

0.69

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over