rs3741775

Variant names:

• chr12-108889827-A-C
• rs3741775
• NM_001917.5:c.386+282A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-108889827-A-C
• chr12-108889827-A-G
• chr12-108889827-A-T

Variant summary

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

The NM_001917.5(DAO):​c.386+282A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,886 control chromosomes in the GnomAD database, including 10,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (10058 hom., cov: 31)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299
• Publications: 22 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-108889827-A-C is Benign according to our data. Variant chr12-108889827-A-C is described in ClinVar as Benign. ClinVar VariationId is 1221443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.386+282A>C		intron_variant	Intron 4 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.386+282A>C		intron_variant	Intron 4 of 10	1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49322 AN: 151768 Hom.: 10061 Cov.: 31

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.325 AC: 49319 AN: 151886 Hom.: 10058 Cov.: 31 AF XY: 0.326 AC XY: 24164 AN XY: 74232

African (AFR) AF: 0.0820 AC: 3399 AN: 41460

American (AMR) AF: 0.283 AC: 4305 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2342 AN: 5138

South Asian (SAS) AF: 0.440 AC: 2113 AN: 4804

European-Finnish (FIN) AF: 0.407 AC: 4288 AN: 10538

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30289 AN: 67928

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.398 Hom.: 6445

Bravo AF: 0.305

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.30
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: rs3741775; hg19: chr12-109283603; COSMIC: COSV57324331;