rs1536142

Positions:

• chr1-58068909-C-T

Variant summary

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

The ENST00000419596.1(ENSG00000235038):​n.170-2641C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,082 control chromosomes in the GnomAD database, including 41,968 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 (41968 hom., cov: 32)
• Consequence: ENST00000419596.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

(HGNC:):

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001353980.2	c.-450-98044G>A		intron_variant			NP_001340909.1
DAB1	NM_001379461.1	c.-375+81602G>A		intron_variant			NP_001366390.1
DAB1	NM_001379462.1	c.-450-98044G>A		intron_variant			NP_001366391.1
DAB1	NM_021080.5	c.-375+181331G>A		intron_variant			NP_066566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000419596.1	n.170-2641C>T		intron_variant, non_coding_transcript_variant		3
DAB1	ENST00000485760.5	n.387+81602G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112627 AN: 151964 Hom.: 41925 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.741 AC: 112725 AN: 152082 Hom.: 41968 Cov.: 32 AF XY: 0.742 AC XY: 55178 AN XY: 74320

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.769

Alfa AF: 0.713 Hom.: 6151

Bravo AF: 0.751

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.6
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: rs1536142; hg19: chr1-58534581;