12-108878275-C-T

Variant names:

• chr12-108878275-C-T
• rs4623951
• ENST00000551281.5:c.-9-6723C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000551281.5(DAO):​c.-9-6723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,884 control chromosomes in the GnomAD database, including 33,799 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 0.66 (33799 hom., cov: 30)
• Consequence: DAO ENST00000551281.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 17 publications found

Genes affected

DAO (HGNC:2671): (D-amino acid oxidase) This gene encodes the peroxisomal enzyme D-amino acid oxidase. The enzyme is a flavoprotein which uses flavin adenine dinucleotide (FAD) as its prosthetic group. Its substrates include a wide variety of D-amino acids, but it is inactive on the naturally occurring L-amino acids. Its biological function is not known; it may act as a detoxifying agent which removes D-amino acids that accumulate during aging. In mice, it degrades D-serine, a co-agonist of the NMDA receptor. This gene may play a role in the pathophysiology of schizophrenia. [provided by RefSeq, Jul 2008]

DAO Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: ClinGen, Orphanet, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551281.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAO	ENST00000551281.5	TSL:1	c.-9-6723C>T		intron	N/A	ENSP00000446853.1
	DAO	ENST00000548052.5	TSL:5	n.349-1288C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100407 AN: 151766 Hom.: 33754 Cov.: 30

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.662 AC: 100513 AN: 151884 Hom.: 33799 Cov.: 30 AF XY: 0.666 AC XY: 49417 AN XY: 74226

African (AFR) AF: 0.759 AC: 31463 AN: 41448

American (AMR) AF: 0.726 AC: 11068 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2193 AN: 3464

East Asian (EAS) AF: 0.796 AC: 4111 AN: 5162

South Asian (SAS) AF: 0.710 AC: 3418 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6046 AN: 10524

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40048 AN: 67902

Other (OTH) AF: 0.655 AC: 1384 AN: 2112

Alfa AF: 0.608 Hom.: 27813

Bravo AF: 0.678

Asia WGS AF: 0.714 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.17
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4623951; hg19: chr12-109272051;