rs4244011

Positions:

• chr1-57663964-G-A

Variant summary

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

The NM_021080.5(DAB1):​c.-210-14299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,008 control chromosomes in the GnomAD database, including 8,609 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 0.33 (8609 hom., cov: 32)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-210-14299C>T		intron_variant
DAB1	NM_001379461.1	c.-210-14299C>T		intron_variant
DAB1	NM_001379462.1	c.-210-14299C>T		intron_variant
DAB1	NM_021080.5	c.-210-14299C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.552-14299C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50126 AN: 151890 Hom.: 8603 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.330 AC: 50144 AN: 152008 Hom.: 8609 Cov.: 32 AF XY: 0.322 AC XY: 23921 AN XY: 74288

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.341

Alfa AF: 0.368 Hom.: 10762

Bravo AF: 0.333

Asia WGS AF: 0.166 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4244011; hg19: chr1-58129636;