rs4947535

Variant names:

• chr7-50463983-T-A
• rs4947535
• NM_001082971.2:c.1243-552A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-50463983-T-A
• chr7-50463983-T-C
• chr7-50463983-T-G

Variant summary

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

The ENST00000444124.7(DDC):​c.1243-552A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,608 control chromosomes in the GnomAD database, including 33,658 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 0.66 (33658 hom., cov: 29)
• Consequence: DDC ENST00000444124.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 12 publications found

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: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444124.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.1243-552A>T		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.1243-552A>T		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.1129-552A>T		intron	N/A	NP_001229815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.1243-552A>T		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.1243-552A>T		intron	N/A	ENSP00000350616.5
	DDC	ENST00000622873.4	TSL:3	c.1129-552A>T		intron	N/A	ENSP00000479110.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100519 AN: 151488 Hom.: 33614 Cov.: 29

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.664 AC: 100629 AN: 151608 Hom.: 33658 Cov.: 29 AF XY: 0.667 AC XY: 49391 AN XY: 74048

African (AFR) AF: 0.606 AC: 25017 AN: 41280

American (AMR) AF: 0.736 AC: 11217 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2390 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2593 AN: 5118

South Asian (SAS) AF: 0.632 AC: 3025 AN: 4784

European-Finnish (FIN) AF: 0.753 AC: 7914 AN: 10516

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.684 AC: 46451 AN: 67902

Other (OTH) AF: 0.660 AC: 1386 AN: 2100

Alfa AF: 0.657 Hom.: 3869

Bravo AF: 0.659

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.32
Mutation Taster		=100/0	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: rs4947535; hg19: chr7-50531681;