NM_001379462.1:c.-450-98044G>A

Variant names:

• chr1-58068909-C-T
• rs1536142
• NM_001379462.1:c.-450-98044G>A

Variant summary

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

The NM_001379462.1(DAB1):​c.-450-98044G>A variant causes a intron 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: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 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)

ENSG00000235038 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.-450-98044G>A		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-375+181331G>A		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-375+81602G>A		intron	N/A	NP_001366390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000235038	ENST00000419596.1	TSL:3	n.170-2641C>T		intron	N/A
	DAB1	ENST00000485760.5	TSL:2	n.387+81602G>A		intron	N/A

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

African (AFR) AF: 0.789 AC: 32765 AN: 41502

American (AMR) AF: 0.755 AC: 11537 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2595 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4375 AN: 5170

South Asian (SAS) AF: 0.782 AC: 3769 AN: 4820

European-Finnish (FIN) AF: 0.669 AC: 7045 AN: 10536

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48111 AN: 67986

Other (OTH) AF: 0.769 AC: 1622 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.6
DANN	Benign	0.66
PhyloP100		0.0
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: rs1536142; hg19: chr1-58534581;