rs1470750

Variant names:

• chr7-50508950-C-G
• rs1470750
• NM_001082971.2:c.715-4891G>C

Variant summary

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

The NM_001082971.2(DDC):​c.715-4891G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,104 control chromosomes in the GnomAD database, including 8,190 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 0.30 (8190 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.715-4891G>C		intron_variant	Intron 6 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.715-4891G>C		intron_variant	Intron 6 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44966 AN: 151986 Hom.: 8185 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.296 AC: 44969 AN: 152104 Hom.: 8190 Cov.: 32 AF XY: 0.289 AC XY: 21487 AN XY: 74368

African (AFR) AF: 0.0766 AC: 3183 AN: 41538

American (AMR) AF: 0.350 AC: 5350 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1259 AN: 5168

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4812

European-Finnish (FIN) AF: 0.307 AC: 3244 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27931 AN: 67962

Other (OTH) AF: 0.343 AC: 725 AN: 2112

Alfa AF: 0.336 Hom.: 1174

Bravo AF: 0.293

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.69
PhyloP100		-0.13
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: rs1470750; hg19: chr7-50576648;