dbSNP rs3918347: DAO:c.912+69A>G (chr12-108899544-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001917.5(DAO):c.912+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,331,902 control chromosomes in the GnomAD database, including 66,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9689 hom., cov: 32)

Exomes 𝑓: 0.30 ( 57181 hom. )

Consequence

DAO
NM_001917.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0350

Publications

21 publications found

Variant links:

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: Ambry Genetics, Genomics England PanelApp, Orphanet, ClinGen

DAO links:

LOC124903011 (HGNC:):

LOC124903011 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-108899544-A-G is Benign according to our data. Variant chr12-108899544-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DAO	NM_001917.5	MANE Select	c.912+69A>G	intron	N/A	NP_001908.3
DAO	NM_001413634.1		c.912+69A>G	intron	N/A	NP_001400563.1	P14920
DAO	NM_001413635.1		c.*38+69A>G	intron	N/A	NP_001400564.1	A0A0S2Z3J4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DAO	ENST00000228476.8	TSL:1 MANE Select	c.912+69A>G	intron	N/A	ENSP00000228476.3	P14920
DAO	ENST00000551281.5	TSL:1	c.714+69A>G	intron	N/A	ENSP00000446853.1	A0A0B4J250
DAO	ENST00000547122.5	TSL:1	n.*560+69A>G	intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52375

AN:

151902

Hom.:

9670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.380

GnomAD4 exome

AF:

0.300

AC:

354430

AN:

1179882

Hom.:

57181

Cov.:

AF XY:

0.302

AC XY:

179731

AN XY:

595262

show subpopulations

African (AFR)

AF:

0.408

AC:

11132

AN:

27252

American (AMR)

AF:

0.570

AC:

21871

AN:

38380

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

7344

AN:

23892

East Asian (EAS)

AF:

0.469

AC:

16656

AN:

35480

South Asian (SAS)

AF:

0.377

AC:

28748

AN:

76236

European-Finnish (FIN)

AF:

0.294

AC:

14278

AN:

48496

Middle Eastern (MID)

AF:

0.421

AC:

2107

AN:

5006

European-Non Finnish (NFE)

AF:

0.270

AC:

236229

AN:

874266

Other (OTH)

AF:

0.316

AC:

16065

AN:

50874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12581

25162

37743

50324

62905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7446

14892

22338

29784

37230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.345

AC:

52456

AN:

152020

Hom.:

9689

Cov.:

AF XY:

0.354

AC XY:

26270

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.399

AC:

16555

AN:

41454

American (AMR)

AF:

0.508

AC:

7757

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1045

AN:

3466

East Asian (EAS)

AF:

0.473

AC:

2444

AN:

5172

South Asian (SAS)

AF:

0.382

AC:

1838

AN:

4808

European-Finnish (FIN)

AF:

0.305

AC:

3221

AN:

10568

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18398

AN:

67974

Other (OTH)

AF:

0.382

AC:

808

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1733

3465

5198

6930

8663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.307

Hom.:

4428

Bravo

AF:

0.365

Asia WGS

AF:

0.415

AC:

1442

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.81

(source)

DANN

Benign

0.78

PhyloP100

-0.035

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over