rs11575461

Variant names:

• chr7-50479485-G-A
• rs11575461
• NM_001082971.2:c.1021+302C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-50479485-G-A
• chr7-50479485-G-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.1021+302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,712 control chromosomes in the GnomAD database, including 22,498 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 0.54 (22498 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.1021+302C>T		intron_variant	Intron 10 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.1021+302C>T		intron_variant	Intron 10 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82195 AN: 151596 Hom.: 22460 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.542 AC: 82294 AN: 151712 Hom.: 22498 Cov.: 33 AF XY: 0.538 AC XY: 39898 AN XY: 74178

African (AFR) AF: 0.493 AC: 20416 AN: 41376

American (AMR) AF: 0.617 AC: 9424 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2118 AN: 3462

East Asian (EAS) AF: 0.441 AC: 2262 AN: 5132

South Asian (SAS) AF: 0.513 AC: 2473 AN: 4820

European-Finnish (FIN) AF: 0.479 AC: 5063 AN: 10560

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38796 AN: 67788

Other (OTH) AF: 0.566 AC: 1194 AN: 2108

Alfa AF: 0.544 Hom.: 2900

Bravo AF: 0.549

Asia WGS AF: 0.526 AC: 1830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.41
PhyloP100		-0.34
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: rs11575461; hg19: chr7-50547183;