rs17041074

Variant names:

• chr12-108898098-G-A
• rs17041074
• NM_001917.5:c.696-581G>A

Variant summary

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

The NM_001917.5(DAO):​c.696-581G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,872 control chromosomes in the GnomAD database, including 9,291 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 0.34 (9291 hom., cov: 31)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 1 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

LOC124903011 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.696-581G>A		intron_variant	Intron 8 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.696-581G>A		intron_variant	Intron 8 of 10	1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51317 AN: 151754 Hom.: 9273 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.338 AC: 51395 AN: 151872 Hom.: 9291 Cov.: 31 AF XY: 0.347 AC XY: 25754 AN XY: 74208

African (AFR) AF: 0.377 AC: 15627 AN: 41408

American (AMR) AF: 0.507 AC: 7730 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1035 AN: 3464

East Asian (EAS) AF: 0.472 AC: 2434 AN: 5162

South Asian (SAS) AF: 0.384 AC: 1846 AN: 4808

European-Finnish (FIN) AF: 0.305 AC: 3210 AN: 10528

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18331 AN: 67938

Other (OTH) AF: 0.378 AC: 796 AN: 2106

Alfa AF: 0.298 Hom.: 911

Bravo AF: 0.358

Asia WGS AF: 0.414 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.83
PhyloP100		0.24
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: rs17041074; hg19: chr12-109291874;