rs11238133

Variant names:

• chr7-50475216-A-C
• rs11238133
• NM_001082971.2:c.1041+1408T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-50475216-A-C
• chr7-50475216-A-T

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+1408T>G 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 152,136 control chromosomes in the GnomAD database, including 35,815 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 (35815 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 13 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.1041+1408T>G		intron_variant	Intron 11 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.1041+1408T>G		intron_variant	Intron 11 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103843 AN: 152016 Hom.: 35762 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.646

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: 103958 AN: 152136 Hom.: 35815 Cov.: 33 AF XY: 0.679 AC XY: 50505 AN XY: 74350

African (AFR) AF: 0.733 AC: 30417 AN: 41520

American (AMR) AF: 0.731 AC: 11175 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2567 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2805 AN: 5174

South Asian (SAS) AF: 0.586 AC: 2823 AN: 4818

European-Finnish (FIN) AF: 0.601 AC: 6356 AN: 10576

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

European-Non Finnish (NFE) AF: 0.670 AC: 45514 AN: 67970

Other (OTH) AF: 0.696 AC: 1467 AN: 2108

Alfa AF: 0.676 Hom.: 50630

Bravo AF: 0.695

Asia WGS AF: 0.609 AC: 2121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.30
PhyloP100		-0.64
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: rs11238133; hg19: chr7-50542914;