chr1-57159976-A-G

Position:

• chr1-57159976-A-G

Variant summary

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

The NM_001365792.1(DAB1):​c.68-14547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,818 control chromosomes in the GnomAD database, including 27,384 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 0.60 (27384 hom., cov: 31)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.68-14547T>C		intron_variant		ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.68-14547T>C		intron_variant		5	NM_001365792.1	ENSP00000360280	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90333 AN: 151700 Hom.: 27369 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.595 AC: 90395 AN: 151818 Hom.: 27384 Cov.: 31 AF XY: 0.587 AC XY: 43554 AN XY: 74160

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.608

Alfa AF: 0.583 Hom.: 29647

Bravo AF: 0.594

Asia WGS AF: 0.537 AC: 1870 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	0.016
DANN	Benign	0.22

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: rs10889028; hg19: chr1-57625649;