rs11581152

Variant names:

• chr1-57518990-G-A
• rs11581152
• NM_001379462.1:c.-137+130602C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379462.1(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_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 1 publications found

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]

DAB1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 37

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001379462.1		c.-137+130602C>T		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-137+130602C>T		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-137+130602C>T		intron	N/A	NP_001366390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000485760.5	TSL:2	n.625+130602C>T		intron	N/A

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

African (AFR) AF: 0.0969 AC: 4015 AN: 41418

American (AMR) AF: 0.151 AC: 2306 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.152 AC: 782 AN: 5154

South Asian (SAS) AF: 0.138 AC: 660 AN: 4794

European-Finnish (FIN) AF: 0.244 AC: 2573 AN: 10534

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16424 AN: 67962

Other (OTH) AF: 0.189 AC: 397 AN: 2104

Alfa AF: 0.214 Hom.: 488

Bravo AF: 0.173

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.72
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11581152; hg19: chr1-57984662;