1-58383563-A-G

Variant names:

• chr1-58383563-A-G
• rs7367176
• NM_001379461.1:c.-504-40160T>C

Variant summary

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

The NM_001379461.1(DAB1):​c.-504-40160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,156 control chromosomes in the GnomAD database, including 42,046 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 0.73 (42046 hom., cov: 32)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.-504-40160T>C		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.258-40160T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111288 AN: 152038 Hom.: 42000 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.732 AC: 111383 AN: 152156 Hom.: 42046 Cov.: 32 AF XY: 0.727 AC XY: 54070 AN XY: 74360

African (AFR) AF: 0.934 AC: 38791 AN: 41550

American (AMR) AF: 0.566 AC: 8655 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2197 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3841 AN: 5178

South Asian (SAS) AF: 0.708 AC: 3411 AN: 4820

European-Finnish (FIN) AF: 0.654 AC: 6902 AN: 10560

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45401 AN: 67976

Other (OTH) AF: 0.705 AC: 1489 AN: 2112

Alfa AF: 0.663 Hom.: 14877

Bravo AF: 0.731

Asia WGS AF: 0.708 AC: 2461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs7367176; hg19: chr1-58849235;