rs701567

Positions:

• chr13-105489646-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375936.9(DAOA):​c.282-255T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 799,876 control chromosomes in the GnomAD database, including 81,367 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 0.50 (20257 hom., cov: 33)
  • Exomes 𝑓: 0.43 (61110 hom.)
• Consequence: DAOA ENST00000375936.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

DAOA (HGNC:21191): (D-amino acid oxidase activator) This gene encodes a protein that may function as an activator of D-amino acid oxidase, which degrades the gliotransmitter D-serine, a potent activator of N-methyl-D-aspartate (NMDA) type glutamate receptors. Studies also suggest that one encoded isoform may play a role in mitochondrial function and dendritic arborization. Polymorphisms in this gene have been implicated in susceptibility to schizophrenia and bipolar affective disorder. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Mar 2011]

DAOA-AS1 (HGNC:30243): (DAOA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAOA	NM_172370.5	c.282-255T>C		intron_variant		ENST00000375936.9	NP_758958.3
DAOA-AS1	NR_040247.1	n.505+130A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.282-255T>C		intron_variant		1	NM_172370.5	ENSP00000365103	P2
DAOA-AS1	ENST00000448407.1	n.505+130A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76040 AN: 151968 Hom.: 20229 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.429 AC: 278175 AN: 647790 Hom.: 61110 AF XY: 0.426 AC XY: 139350 AN XY: 327398

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.501 AC: 76121 AN: 152086 Hom.: 20257 Cov.: 33 AF XY: 0.495 AC XY: 36825 AN XY: 74348

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.476

Alfa AF: 0.438 Hom.: 19687

Bravo AF: 0.510

Asia WGS AF: 0.409 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.92
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs701567; hg19: chr13-106141995;