NM_001379462.1:c.-450-41262C>A

Variant names:

• chr1-58012127-G-T
• rs1188008
• NM_001379462.1:c.-450-41262C>A

Variant summary

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

The NM_001379462.1(DAB1):​c.-450-41262C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,048 control chromosomes in the GnomAD database, including 27,252 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 0.59 (27252 hom., cov: 33)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-450-41262C>A		intron_variant	Intron 1 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-374-127965C>A		intron_variant	Intron 1 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-374-127965C>A		intron_variant	Intron 5 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-450-41262C>A		intron_variant	Intron 1 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.388-127965C>A		intron_variant	Intron 5 of 20	2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89350 AN: 151930 Hom.: 27224 Cov.: 33

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.588 AC: 89435 AN: 152048 Hom.: 27252 Cov.: 33 AF XY: 0.603 AC XY: 44783 AN XY: 74322

African (AFR) AF: 0.666 AC: 27633 AN: 41470

American (AMR) AF: 0.601 AC: 9179 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1681 AN: 3468

East Asian (EAS) AF: 0.976 AC: 5051 AN: 5176

South Asian (SAS) AF: 0.786 AC: 3781 AN: 4812

European-Finnish (FIN) AF: 0.625 AC: 6604 AN: 10570

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33533 AN: 67968

Other (OTH) AF: 0.591 AC: 1242 AN: 2102

Alfa AF: 0.522 Hom.: 12855

Bravo AF: 0.587

Asia WGS AF: 0.847 AC: 2942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.76
PhyloP100		0.029
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: rs1188008; hg19: chr1-58477799;