rs3131755

chr1-57678538-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.-210-28873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,996 control chromosomes in the GnomAD database, including 42,179 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 0.74 (42179 hom., cov: 30)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-210-28873T>C		intron_variant
DAB1	NM_001379461.1	c.-210-28873T>C		intron_variant
DAB1	NM_001379462.1	c.-210-28873T>C		intron_variant
DAB1	NM_021080.5	c.-210-28873T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.552-28873T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111872 AN: 151878 Hom.: 42122 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.737 AC: 111989 AN: 151996 Hom.: 42179 Cov.: 30 AF XY: 0.742 AC XY: 55097 AN XY: 74262

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.716

Alfa AF: 0.634 Hom.: 21471

Bravo AF: 0.743

Asia WGS AF: 0.859 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3131755; hg19: chr1-58144210;