NM_001379462.1:c.-374-12289G>A

Variant names:

• chr1-57896451-C-T
• rs1202835
• NM_001379462.1:c.-374-12289G>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.-374-12289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,704 control chromosomes in the GnomAD database, including 2,661 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 0.17 (2661 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-374-12289G>A		intron_variant	Intron 2 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-374-12289G>A		intron_variant	Intron 1 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-374-12289G>A		intron_variant	Intron 5 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-374-12289G>A		intron_variant	Intron 2 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.388-12289G>A		intron_variant	Intron 5 of 20	2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26149 AN: 151602 Hom.: 2658 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.172 AC: 26163 AN: 151704 Hom.: 2661 Cov.: 32 AF XY: 0.171 AC XY: 12672 AN XY: 74106

African (AFR) AF: 0.0787 AC: 3257 AN: 41410

American (AMR) AF: 0.273 AC: 4159 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.0661 AC: 341 AN: 5160

South Asian (SAS) AF: 0.169 AC: 812 AN: 4794

European-Finnish (FIN) AF: 0.164 AC: 1711 AN: 10408

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.212 AC: 14385 AN: 67912

Other (OTH) AF: 0.181 AC: 381 AN: 2104

Alfa AF: 0.102 Hom.: 177

Bravo AF: 0.177

Asia WGS AF: 0.135 AC: 471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.47
PhyloP100		-0.88
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: rs1202835; hg19: chr1-58362123;