rs3823674

Variant names:

• chr7-50504298-C-T
• rs3823674
• NM_001082971.2:c.715-239G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-50504298-C-T
• chr7-50504298-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082971.2(DDC):​c.715-239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,978 control chromosomes in the GnomAD database, including 11,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11526 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 13 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-50504298-C-T is Benign according to our data. Variant chr7-50504298-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.715-239G>A		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.715-239G>A		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.601-239G>A		intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.715-239G>A		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.715-239G>A		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.715-239G>A		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58669 AN: 151860 Hom.: 11515 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.386 AC: 58716 AN: 151978 Hom.: 11526 Cov.: 33 AF XY: 0.380 AC XY: 28248 AN XY: 74292

African (AFR) AF: 0.312 AC: 12941 AN: 41452

American (AMR) AF: 0.387 AC: 5919 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5168

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4816

European-Finnish (FIN) AF: 0.378 AC: 3988 AN: 10548

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29323 AN: 67944

Other (OTH) AF: 0.409 AC: 861 AN: 2104

Alfa AF: 0.295 Hom.: 1103

Bravo AF: 0.386

Asia WGS AF: 0.396 AC: 1380 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.28
PhyloP100		-1.5
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: rs3823674; hg19: chr7-50571996;