7-50475181-C-T

Variant names:

• chr7-50475181-C-T
• rs11761683
• NM_001082971.2:c.1041+1443G>A

Variant summary

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

The NM_001082971.2(DDC):​c.1041+1443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,104 control chromosomes in the GnomAD database, including 35,810 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 0.68 (35810 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 7 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.1041+1443G>A		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.1041+1443G>A		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.927+1443G>A		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.1041+1443G>A		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.1041+1443G>A		intron	N/A	ENSP00000350616.5
	DDC	ENST00000622873.4	TSL:3	c.927+1443G>A		intron	N/A	ENSP00000479110.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103850 AN: 151986 Hom.: 35758 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.683 AC: 103963 AN: 152104 Hom.: 35810 Cov.: 32 AF XY: 0.680 AC XY: 50524 AN XY: 74348

African (AFR) AF: 0.733 AC: 30390 AN: 41476

American (AMR) AF: 0.731 AC: 11174 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2807 AN: 5168

South Asian (SAS) AF: 0.586 AC: 2826 AN: 4822

European-Finnish (FIN) AF: 0.602 AC: 6360 AN: 10560

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45534 AN: 67996

Other (OTH) AF: 0.696 AC: 1472 AN: 2114

Alfa AF: 0.683 Hom.: 6175

Bravo AF: 0.695

Asia WGS AF: 0.609 AC: 2120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.68
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11761683; hg19: chr7-50542879;