rs10493251

Positions:

• chr1-58298409-C-T

Variant summary

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

The NM_001379461.1(DAB1):​c.-453+44943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,102 control chromosomes in the GnomAD database, including 5,176 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 0.24 (5176 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-453+44943G>A		intron_variant			NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.309+44943G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36210 AN: 151984 Hom.: 5162 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.238 AC: 36233 AN: 152102 Hom.: 5176 Cov.: 33 AF XY: 0.249 AC XY: 18533 AN XY: 74336

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.260

Alfa AF: 0.263 Hom.: 2591

Bravo AF: 0.225

Asia WGS AF: 0.357 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10493251; hg19: chr1-58764081;