rs1451371

Variant names:

• chr7-50485353-T-C
• rs1451371
• NM_001082971.2:c.945-5490A>G

Variant summary

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

The NM_001082971.2(DDC):​c.945-5490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,084 control chromosomes in the GnomAD database, including 12,893 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 0.41 (12893 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.945-5490A>G		intron_variant	Intron 9 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.945-5490A>G		intron_variant	Intron 9 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61592 AN: 151968 Hom.: 12869 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.405 AC: 61653 AN: 152084 Hom.: 12893 Cov.: 33 AF XY: 0.403 AC XY: 29980 AN XY: 74336

African (AFR) AF: 0.299 AC: 12426 AN: 41516

American (AMR) AF: 0.513 AC: 7837 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1820 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2278 AN: 5168

South Asian (SAS) AF: 0.360 AC: 1735 AN: 4816

European-Finnish (FIN) AF: 0.394 AC: 4154 AN: 10556

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30009 AN: 67954

Other (OTH) AF: 0.434 AC: 918 AN: 2114

Alfa AF: 0.405 Hom.: 6923

Bravo AF: 0.411

Asia WGS AF: 0.439 AC: 1519 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.78
PhyloP100		0.15
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: rs1451371; hg19: chr7-50553051;