rs3757472

Variant names:

• chr7-50470285-A-C
• rs3757472
• NM_001082971.2:c.1042-114T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-50470285-A-C
• chr7-50470285-A-G
• chr7-50470285-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.1042-114T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 785,856 control chromosomes in the GnomAD database, including 179,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33811 hom., cov: 33)
  • Exomes 𝑓: 0.68 (145864 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.494
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-50470285-A-C is Benign according to our data. Variant chr7-50470285-A-C is described in ClinVar as Benign. ClinVar VariationId is 1245994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 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.1042-114T>G		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.1042-114T>G		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.928-114T>G		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.1042-114T>G		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.1042-114T>G		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000897740.1		c.1186-114T>G		intron	N/A	ENSP00000567799.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100918 AN: 152100 Hom.: 33767 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.676 AC: 428028 AN: 633638 Hom.: 145864 AF XY: 0.671 AC XY: 230332 AN XY: 343042

African (AFR) AF: 0.607 AC: 10576 AN: 17412

American (AMR) AF: 0.791 AC: 31968 AN: 40392

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 14356 AN: 20846

East Asian (EAS) AF: 0.520 AC: 17755 AN: 34166

South Asian (SAS) AF: 0.631 AC: 42568 AN: 67448

European-Finnish (FIN) AF: 0.741 AC: 28590 AN: 38590

Middle Eastern (MID) AF: 0.541 AC: 2267 AN: 4194

European-Non Finnish (NFE) AF: 0.683 AC: 257770 AN: 377170

Other (OTH) AF: 0.664 AC: 22178 AN: 33420

GnomAD4 genome AF: 0.664 AC: 101026 AN: 152218 Hom.: 33811 Cov.: 33 AF XY: 0.668 AC XY: 49680 AN XY: 74424

African (AFR) AF: 0.604 AC: 25074 AN: 41524

American (AMR) AF: 0.737 AC: 11271 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2686 AN: 5174

South Asian (SAS) AF: 0.632 AC: 3044 AN: 4818

European-Finnish (FIN) AF: 0.752 AC: 7984 AN: 10614

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46549 AN: 68002

Other (OTH) AF: 0.657 AC: 1388 AN: 2112

Alfa AF: 0.665 Hom.: 51957

Bravo AF: 0.659

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.49
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: rs3757472; hg19: chr7-50537983; COSMIC: COSV63567991;