rs534455

Positions:

• chr1-57059439-C-G
• chr1-57059439-C-T

Variant summary

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

The NM_001365792.1(DAB1):​c.723+3445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,960 control chromosomes in the GnomAD database, including 28,283 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 0.61 (28283 hom., cov: 31)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.723+3445G>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.723+3445G>C		intron_variant		5	NM_001365792.1	ENSP00000360280	P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91978 AN: 151842 Hom.: 28272 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.606 AC: 92028 AN: 151960 Hom.: 28283 Cov.: 31 AF XY: 0.598 AC XY: 44369 AN XY: 74252

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.637

Alfa AF: 0.515 Hom.: 1450

Bravo AF: 0.600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.37

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: rs534455; hg19: chr1-57525112;