Genetic Variant ENST00000457412.6:n.374C>A (chr1-57880535-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000457412.6(DAB1-AS1):n.374C>A 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 0.125 in 152,134 control chromosomes in the GnomAD database, including 1,382 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 0.13 ( 1382 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DAB1-AS1
ENST00000457412.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

3 publications found

Variant links:

Genes affected

DAB1-AS1 (HGNC:49443): (DAB1 antisense RNA 1)

DAB1-AS1 links:

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
DAB1	NM_001379462.1 link	c.-211+3464G>T	intron_variant	Intron 3 of 17	NP_001366391.1
DAB1	NM_021080.5 link	c.-211+3464G>T	intron_variant	Intron 2 of 16	NP_066566.3	O75553-6
DAB1	NM_001379461.1 link	c.-211+3464G>T	intron_variant	Intron 6 of 20	NP_001366390.1
DAB1	NM_001353980.2 link	c.-211+3464G>T	intron_variant	Intron 3 of 5	NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
DAB1-AS1	ENST00000457412.6 link	n.374C>A	non_coding_transcript_exon_variant	Exon 4 of 4	5
DAB1-AS1	ENST00000586465.5 link	n.552C>A	non_coding_transcript_exon_variant	Exon 6 of 6	5
DAB1-AS1	ENST00000591173.5 link	n.525C>A	non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19032

AN:

152016

Hom.:

1382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0794

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0900

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.139

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

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)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.125

AC:

19044

AN:

152134

Hom.:

1382

Cov.:

AF XY:

0.124

AC XY:

9206

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0794

AC:

3296

AN:

41498

American (AMR)

AF:

0.101

AC:

1545

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1379

AN:

5152

South Asian (SAS)

AF:

0.136

AC:

658

AN:

4822

European-Finnish (FIN)

AF:

0.0900

AC:

954

AN:

10602

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10046

AN:

67990

Other (OTH)

AF:

0.140

AC:

296

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

825

1649

2474

3298

4123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.144

Hom.:

7189

Bravo

AF:

0.123

Asia WGS

AF:

0.185

AC:

643

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.78

PhyloP100

-1.1

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