1-58360498-G-C

Variant names:

• chr1-58360498-G-C
• rs1341743
• NM_001379461.1:c.-504-17095C>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.-504-17095C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 152,054 control chromosomes in the GnomAD database, including 603 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 0.083 (603 hom., cov: 32)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.-504-17095C>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.258-17095C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12658 AN: 151936 Hom.: 605 Cov.: 32

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0833 AC: 12660 AN: 152054 Hom.: 603 Cov.: 32 AF XY: 0.0818 AC XY: 6083 AN XY: 74326

African (AFR) AF: 0.0882 AC: 3656 AN: 41472

American (AMR) AF: 0.0978 AC: 1493 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1106 AN: 5150

South Asian (SAS) AF: 0.0938 AC: 451 AN: 4810

European-Finnish (FIN) AF: 0.0344 AC: 364 AN: 10580

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5204 AN: 67992

Other (OTH) AF: 0.0746 AC: 157 AN: 2104

Alfa AF: 0.0157 Hom.: 14

Bravo AF: 0.0872

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs1341743; hg19: chr1-58826170;