1-57375990-C-T

Position:

• chr1-57375990-C-T

Variant summary

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

The NM_001365792.1(DAB1):​c.-137+47940G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,948 control chromosomes in the GnomAD database, including 12,984 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 0.41 (12984 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.-137+47940G>A		intron_variant		ENST00000371236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.-137+47940G>A		intron_variant		5	NM_001365792.1	P1
DAB1	ENST00000371230.1	c.-137+47940G>A		intron_variant		5
DAB1	ENST00000485760.5	n.626-84824G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61520 AN: 151828 Hom.: 12968 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.405 AC: 61579 AN: 151948 Hom.: 12984 Cov.: 32 AF XY: 0.397 AC XY: 29463 AN XY: 74254

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.414

Alfa AF: 0.422 Hom.: 27679

Bravo AF: 0.405

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10047071; hg19: chr1-57841662;