rs1188006

chr1-58011340-G-Achr1-58011340-G-Cchr1-58011340-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021080.5(DAB1):c.-374-127178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,110 control chromosomes in the GnomAD database, including 12,436 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 0.40 (12436 hom., cov: 33)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-450-40475C>T		intron_variant
DAB1	NM_001379461.1	c.-374-127178C>T		intron_variant
DAB1	NM_001379462.1	c.-450-40475C>T		intron_variant
DAB1	NM_021080.5	c.-374-127178C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.388-127178C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60488 AN: 151992 Hom.: 12437 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.398 AC: 60501 AN: 152110 Hom.: 12436 Cov.: 33 AF XY: 0.405 AC XY: 30122 AN XY: 74360

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.422

Alfa AF: 0.380 Hom.: 1367

Bravo AF: 0.393

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1188006; hg19: chr1-58477012;