rs1556585

chr1-57425089-A-G

Variant summary

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

The NM_021080.5(DAB1):c.-136-133923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,034 control chromosomes in the GnomAD database, including 8,005 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 0.32 (8005 hom., cov: 32)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-136-133923T>C		intron_variant
DAB1	NM_001379461.1	c.-136-133923T>C		intron_variant
DAB1	NM_001379462.1	c.-136-133923T>C		intron_variant
DAB1	NM_021080.5	c.-136-133923T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.626-133923T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47939 AN: 151916 Hom.: 8002 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.315 AC: 47963 AN: 152034 Hom.: 8005 Cov.: 32 AF XY: 0.306 AC XY: 22736 AN XY: 74306

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.0747

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.296

Alfa AF: 0.350 Hom.: 1950

Bravo AF: 0.313

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.2
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: rs1556585; hg19: chr1-57890761;