rs1451375

Variant names:

• chr7-50555014-C-A
• rs1451375
• NM_001082971.2:c.-29+10271G>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.-29+10271G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,934 control chromosomes in the GnomAD database, including 8,532 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 0.32 (8532 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 25 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-29+10271G>T		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-29+10271G>T		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48821 AN: 151816 Hom.: 8522 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.321 AC: 48837 AN: 151934 Hom.: 8532 Cov.: 31 AF XY: 0.333 AC XY: 24728 AN XY: 74234

African (AFR) AF: 0.220 AC: 9132 AN: 41444

American (AMR) AF: 0.255 AC: 3891 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1011 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2485 AN: 5130

South Asian (SAS) AF: 0.462 AC: 2221 AN: 4806

European-Finnish (FIN) AF: 0.534 AC: 5633 AN: 10554

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23468 AN: 67930

Other (OTH) AF: 0.299 AC: 630 AN: 2108

Alfa AF: 0.332 Hom.: 17811

Bravo AF: 0.296

Asia WGS AF: 0.419 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.14
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: rs1451375; hg19: chr7-50622712;