chr7-50475181-C-T

Position:

• chr7-50475181-C-T

Variant summary

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

The NM_001082971.2(DDC):​c.1041+1443G>A 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 152,104 control chromosomes in the GnomAD database, including 35,810 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 (35810 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30

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=-1.04).
• 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/exons	MANE	UniProt
DDC	NM_001082971.2	c.1041+1443G>A		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.1041+1443G>A		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103850 AN: 151986 Hom.: 35758 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.649

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: 103963 AN: 152104 Hom.: 35810 Cov.: 32 AF XY: 0.680 AC XY: 50524 AN XY: 74348

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.696

Alfa AF: 0.681 Hom.: 5952

Bravo AF: 0.695

Asia WGS AF: 0.609 AC: 2120 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	0.12
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11761683; hg19: chr7-50542879;