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GeneBe

1-57015055-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001365792.1(DAB1):c.1272G>A(p.Pro424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

DAB1
NM_001365792.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.62
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-57015055-C-T is Benign according to our data. Variant chr1-57015055-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058113.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.62 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 52 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DAB1NM_001365792.1 linkuse as main transcriptc.1272G>A p.Pro424= synonymous_variant 12/15 ENST00000371236.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DAB1ENST00000371236.7 linkuse as main transcriptc.1272G>A p.Pro424= synonymous_variant 12/155 NM_001365792.1 P1O75553-6

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000342
AC:
52
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000893
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000590
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251366
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000773
AC:
113
AN:
1461834
Hom.:
0
Cov.:
32
AF XY:
0.0000784
AC XY:
57
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000225
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000342
AC:
52
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.000890
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000228
Hom.:
0
Bravo
AF:
0.000446
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DAB1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 27, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.41
Dann
Benign
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144727413; hg19: chr1-57480728; API