1-57733095-C-T

Position:

• chr1-57733095-C-T

Variant summary

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

The NM_021080.5(DAB1):​c.-210-83430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,684 control chromosomes in the GnomAD database, including 3,748 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 0.20 (3748 hom., cov: 31)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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 = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-210-83430G>A		intron_variant
DAB1	NM_001379461.1	c.-210-83430G>A		intron_variant
DAB1	NM_001379462.1	c.-210-83430G>A		intron_variant
DAB1	NM_021080.5	c.-210-83430G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.552-83430G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29767 AN: 151566 Hom.: 3744 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.196 AC: 29802 AN: 151684 Hom.: 3748 Cov.: 31 AF XY: 0.195 AC XY: 14456 AN XY: 74100

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.164

Alfa AF: 0.151 Hom.: 1160

Bravo AF: 0.206

Asia WGS AF: 0.270 AC: 938 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	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3131729; hg19: chr1-58198767;