chr1-58298409-C-T

Variant names:

• chr1-58298409-C-T
• rs10493251
• NM_001379461.1:c.-453+44943G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001379461.1(DAB1):​c.-453+44943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,102 control chromosomes in the GnomAD database, including 5,176 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 0.24 (5176 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379461.1. 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_001379461.1		c.-453+44943G>A		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.309+44943G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36210 AN: 151984 Hom.: 5162 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.238 AC: 36233 AN: 152102 Hom.: 5176 Cov.: 33 AF XY: 0.249 AC XY: 18533 AN XY: 74336

African (AFR) AF: 0.0913 AC: 3795 AN: 41544

American (AMR) AF: 0.299 AC: 4567 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3472

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5168

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4818

European-Finnish (FIN) AF: 0.399 AC: 4210 AN: 10546

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18302 AN: 67964

Other (OTH) AF: 0.260 AC: 550 AN: 2114

Alfa AF: 0.260 Hom.: 2875

Bravo AF: 0.225

Asia WGS AF: 0.357 AC: 1238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.55

Splicing

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

Other links and lift over

dbSNP: rs10493251; hg19: chr1-58764081;