rs864250

Positions:

• chr1-58150560-A-G
• chr1-58150560-A-T

Variant summary

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

The NM_001379461.1(DAB1):​c.-424T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 150,898 control chromosomes in the GnomAD database, including 26,131 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 0.55 (26131 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: DAB1 NM_001379461.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-424T>C		5_prime_UTR_variant	5/21		NP_001366390.1
DAB1	NM_001353980.2	c.-451+99680T>C		intron_variant			NP_001340909.1
DAB1	NM_001379462.1	c.-451+99680T>C		intron_variant			NP_001366391.1
DAB1	NM_021080.5	c.-375+99680T>C		intron_variant			NP_066566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.338T>C		non_coding_transcript_exon_variant	5/21	2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82356 AN: 150788 Hom.: 26077 Cov.: 28

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.487

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.546 AC: 82465 AN: 150898 Hom.: 26131 Cov.: 28 AF XY: 0.556 AC XY: 40930 AN XY: 73614

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.489

Alfa AF: 0.398 Hom.: 12681

Bravo AF: 0.568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.6
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs864250; hg19: chr1-58616232;