dbSNP rs1109896: 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

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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