1-57518990-G-A

Position:

• chr1-57518990-G-A

Variant summary

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

The NM_021080.5(DAB1):​c.-137+130602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,900 control chromosomes in the GnomAD database, including 2,898 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 0.19 (2898 hom., cov: 32)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001353980.2	c.-137+130602C>T		intron_variant			NP_001340909.1
DAB1	NM_001379461.1	c.-137+130602C>T		intron_variant			NP_001366390.1
DAB1	NM_001379462.1	c.-137+130602C>T		intron_variant			NP_001366391.1
DAB1	NM_021080.5	c.-137+130602C>T		intron_variant			NP_066566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.625+130602C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28083 AN: 151784 Hom.: 2895 Cov.: 32

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.185 AC: 28112 AN: 151900 Hom.: 2898 Cov.: 32 AF XY: 0.184 AC XY: 13643 AN XY: 74226

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.189

Alfa AF: 0.219 Hom.: 487

Bravo AF: 0.173

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11581152; hg19: chr1-57984662;