Genetic Variant ENST00000485760.5:n.338T>C (chr1-58150560-A-G) – 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.338T>C 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 0.546 in 150,898 control chromosomes in the GnomAD database, including 26,131 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 0.55 ( 26131 hom., cov: 28)

Failed GnomAD Quality Control

Consequence

DAB1
ENST00000485760.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.506

Publications

4 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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 37
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

DAB1 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=-0.52).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
DAB1	NM_001379461.1 link	c.-424T>C	5_prime_UTR_variant	Exon 5 of 21	NP_001366390.1
DAB1	NM_001379462.1 link	c.-451+99680T>C	intron_variant	Intron 1 of 17	NP_001366391.1
DAB1	NM_021080.5 link	c.-375+99680T>C	intron_variant	Intron 1 of 16	NP_066566.3	O75553-6
DAB1	NM_001353980.2 link	c.-451+99680T>C	intron_variant	Intron 1 of 5	NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5 link	n.338T>C		non_coding_transcript_exon_variant	Exon 5 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82356

AN:

150788

Hom.:

26077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.487

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.546

AC:

82465

AN:

150898

Hom.:

26131

Cov.:

AF XY:

0.556

AC XY:

40930

AN XY:

73614

show subpopulations

African (AFR)

AF:

0.847

AC:

34834

AN:

41108

American (AMR)

AF:

0.559

AC:

8496

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1395

AN:

3466

East Asian (EAS)

AF:

0.858

AC:

4418

AN:

5150

South Asian (SAS)

AF:

0.567

AC:

2698

AN:

4756

European-Finnish (FIN)

AF:

0.485

AC:

4954

AN:

10206

Middle Eastern (MID)

AF:

0.360

AC:

103

AN:

286

European-Non Finnish (NFE)

AF:

0.359

AC:

24290

AN:

67730

Other (OTH)

AF:

0.489

AC:

1024

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1463

2926

4390

5853

7316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<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:

0.420

Hom.:

18892

Bravo

AF:

0.568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.6

(source)

DANN

Benign

0.64

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over