7-50493846-G-A

Position:

• chr7-50493846-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):​c.944+1504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,832 control chromosomes in the GnomAD database, including 45,366 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 0.77 (45366 hom., cov: 30)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.944+1504C>T		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.944+1504C>T		intron_variant		1	NM_001082971.2	ENSP00000403644	P1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 116961 AN: 151714 Hom.: 45310 Cov.: 30

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.771 AC: 117077 AN: 151832 Hom.: 45366 Cov.: 30 AF XY: 0.772 AC XY: 57279 AN XY: 74204

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.772

Alfa AF: 0.768 Hom.: 5581

Bravo AF: 0.773

Asia WGS AF: 0.662 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs7790758; hg19: chr7-50561544;