rs12023109

chr1-58017271-T-G

Variant summary

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

The NM_021080.5(DAB1):c.-374-133109A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00988 in 152,160 control chromosomes in the GnomAD database, including 50 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 0.0099 (50 hom., cov: 31)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-450-46406A>C		intron_variant
DAB1	NM_001379461.1	c.-374-133109A>C		intron_variant
DAB1	NM_001379462.1	c.-450-46406A>C		intron_variant
DAB1	NM_021080.5	c.-374-133109A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.388-133109A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00991 AC: 1506 AN: 152042 Hom.: 50 Cov.: 31

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00592

Gnomad OTH AF: 0.00764

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

GnomAD4 genome AF: 0.00988 AC: 1504 AN: 152160 Hom.: 50 Cov.: 31 AF XY: 0.0111 AC XY: 825 AN XY: 74380

Gnomad4 AFR AF: 0.00195

Gnomad4 AMR AF: 0.00740

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0913

Gnomad4 SAS AF: 0.0713

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.00593

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00693 Hom.: 0

Bravo AF: 0.00922

Asia WGS AF: 0.0660 AC: 229 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.1
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: rs12023109; hg19: chr1-58482943;