rs1188006

Variant names:

• chr1-58011340-G-A
• rs1188006
• NM_001379462.1:c.-450-40475C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-58011340-G-A
• chr1-58011340-G-C
• chr1-58011340-G-T

Variant summary

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

The NM_021080.5(DAB1):​c.-374-127178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,110 control chromosomes in the GnomAD database, including 12,436 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 0.40 (12436 hom., cov: 33)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021080.5. 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.-450-40475C>T		intron	N/A	NP_001366391.1	O75553-6
	DAB1	NM_021080.5		c.-374-127178C>T		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-374-127178C>T		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.388-127178C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60488 AN: 151992 Hom.: 12437 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.398 AC: 60501 AN: 152110 Hom.: 12436 Cov.: 33 AF XY: 0.405 AC XY: 30122 AN XY: 74360

African (AFR) AF: 0.379 AC: 15715 AN: 41502

American (AMR) AF: 0.392 AC: 6001 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1240 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3289 AN: 5162

South Asian (SAS) AF: 0.603 AC: 2897 AN: 4808

European-Finnish (FIN) AF: 0.400 AC: 4233 AN: 10580

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25782 AN: 67972

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.379 Hom.: 1417

Bravo AF: 0.393

Asia WGS AF: 0.618 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.0030
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: rs1188006; hg19: chr1-58477012;