rs1213659

chr1-58361374-C-Achr1-58361374-C-Gchr1-58361374-C-T

Variant summary

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

The NM_001379461.1(DAB1):c.-504-17971G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,348 control chromosomes in the GnomAD database, including 64,620 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 0.92 (64620 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001379461.1	c.-504-17971G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.258-17971G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.920 AC: 140024 AN: 152230 Hom.: 64566 Cov.: 33

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.920 AC: 140133 AN: 152348 Hom.: 64620 Cov.: 33 AF XY: 0.922 AC XY: 68706 AN XY: 74488

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.880

Gnomad4 OTH AF: 0.913

Alfa AF: 0.914 Hom.: 6777

Bravo AF: 0.925

Asia WGS AF: 0.934 AC: 3247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.7
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1213659; hg19: chr1-58827046;