NM_001365792.1:c.68-21385C>T

Variant names:

• chr1-57166814-G-A
• rs155288
• NM_001365792.1:c.68-21385C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365792.1(DAB1):​c.68-21385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,004 control chromosomes in the GnomAD database, including 23,383 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 0.54 (23383 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 3 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.68-21385C>T		intron_variant	Intron 2 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.68-21385C>T		intron_variant	Intron 2 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81497 AN: 151888 Hom.: 23350 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81585 AN: 152004 Hom.: 23383 Cov.: 32 AF XY: 0.530 AC XY: 39406 AN XY: 74290

African (AFR) AF: 0.743 AC: 30811 AN: 41488

American (AMR) AF: 0.377 AC: 5749 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2795 AN: 5158

South Asian (SAS) AF: 0.493 AC: 2373 AN: 4814

European-Finnish (FIN) AF: 0.459 AC: 4842 AN: 10550

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31660 AN: 67946

Other (OTH) AF: 0.526 AC: 1108 AN: 2106

Alfa AF: 0.482 Hom.: 10892

Bravo AF: 0.537

Asia WGS AF: 0.511 AC: 1777 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.19
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs155288; hg19: chr1-57632487;