rs1504589

chr1-57179628-C-Achr1-57179628-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001365792.1(DAB1):c.68-34199G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,956 control chromosomes in the GnomAD database, including 9,334 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 0.32 (9334 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

LOC105378747 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.68-34199G>T		intron_variant		ENST00000371236.7
LOC105378747	XR_007066125.1	n.2541-342C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.68-34199G>T		intron_variant		5	NM_001365792.1	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48130 AN: 151836 Hom.: 9336 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.317 AC: 48124 AN: 151956 Hom.: 9334 Cov.: 32 AF XY: 0.316 AC XY: 23450 AN XY: 74246

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.347

Alfa AF: 0.410 Hom.: 22444

Bravo AF: 0.293

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	17
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs1504589; hg19: chr1-57645301;