1-58292243-T-C

Variant names:

• chr1-58292243-T-C
• rs527409
• NM_001379461.1:c.-453+51109A>G

Variant summary

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

The NM_001379461.1(DAB1):​c.-453+51109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 152,214 control chromosomes in the GnomAD database, including 68,552 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 0.95 (68552 hom., cov: 30)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94
• Publications: 12 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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+51109A>G		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+51109A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144344 AN: 152096 Hom.: 68503 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.949 AC: 144452 AN: 152214 Hom.: 68552 Cov.: 30 AF XY: 0.950 AC XY: 70700 AN XY: 74414

African (AFR) AF: 0.943 AC: 39159 AN: 41534

American (AMR) AF: 0.968 AC: 14799 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5096 AN: 5176

South Asian (SAS) AF: 0.979 AC: 4720 AN: 4822

European-Finnish (FIN) AF: 0.933 AC: 9881 AN: 10588

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64319 AN: 68014

Other (OTH) AF: 0.951 AC: 2012 AN: 2116

Alfa AF: 0.947 Hom.: 161338

Bravo AF: 0.950

Asia WGS AF: 0.976 AC: 3395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.51
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs527409; hg19: chr1-58757915;