NM_001379462.1:c.-450-120061A>G

Variant names:

• chr1-58090926-T-C
• rs873989
• NM_001379462.1:c.-450-120061A>G

Variant summary

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

The NM_001379462.1(DAB1):​c.-450-120061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,098 control chromosomes in the GnomAD database, including 6,210 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 0.26 (6210 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001379462.1		c.-450-120061A>G		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-375+159314A>G		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-375+59585A>G		intron	N/A	NP_001366390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000485760.5	TSL:2	n.387+59585A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39394 AN: 151980 Hom.: 6188 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.259 AC: 39451 AN: 152098 Hom.: 6210 Cov.: 32 AF XY: 0.264 AC XY: 19650 AN XY: 74358

African (AFR) AF: 0.426 AC: 17681 AN: 41458

American (AMR) AF: 0.184 AC: 2820 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2037 AN: 5164

South Asian (SAS) AF: 0.294 AC: 1413 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2737 AN: 10582

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11566 AN: 68006

Other (OTH) AF: 0.235 AC: 496 AN: 2110

Alfa AF: 0.196 Hom.: 10899

Bravo AF: 0.259

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		0.31
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: rs873989; hg19: chr1-58556598;