Genetic Variant DAB1:n.3T>G (chr1-58546732-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000485760.5(DAB1):n.3T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,124 control chromosomes in the GnomAD database, including 34,186 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 0.65 ( 34128 hom., cov: 31)

Exomes 𝑓: 0.70 ( 58 hom. )

Consequence

DAB1
ENST00000485760.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.422

Publications

14 publications found

Variant links:

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 links:

OMA1 (HGNC:29661): (OMA1 zinc metallopeptidase) Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

OMA1 links:

ENSG00000286918 (HGNC:):

ENSG00000286918 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OMA1	NM_145243.5 link	c.-46T>G		upstream_gene_variant		ENST00000371226.8	NP_660286.1	Q96E52-1
DAB1	NM_001379461.1 link	c.-759T>G		upstream_gene_variant			NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMA1	ENST00000371226.8 link	c.-46T>G		upstream_gene_variant		1	NM_145243.5	ENSP00000360270.3		Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98598

AN:

151784

Hom.:

34115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.667

GnomAD4 exome

AF:

0.703

AC:

156

AN:

222

Hom.:

Cov.:

AF XY:

0.728

AC XY:

131

AN XY:

180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.681

AC:

128

AN:

188

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.649

AC:

98633

AN:

151902

Hom.:

34128

Cov.:

AF XY:

0.662

AC XY:

49137

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.392

AC:

16214

AN:

41374

American (AMR)

AF:

0.753

AC:

11500

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2477

AN:

3470

East Asian (EAS)

AF:

0.945

AC:

4845

AN:

5128

South Asian (SAS)

AF:

0.803

AC:

3864

AN:

4810

European-Finnish (FIN)

AF:

0.820

AC:

8669

AN:

10578

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48951

AN:

67946

Other (OTH)

AF:

0.671

AC:

1417

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.668

Hom.:

8374

Bravo

AF:

0.633

Asia WGS

AF:

0.841

AC:

2924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.6

(source)

DANN

Benign

0.82

PhyloP100

-0.42

PromoterAI

0.070

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over