rs1325445

Variant names:

• chr1-58001703-C-T
• rs1325445
• NM_001379462.1:c.-450-30838G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001379462.1(DAB1):​c.-450-30838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 152,260 control chromosomes in the GnomAD database, including 30 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 0.016 (30 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• 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=-0.9).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.016 (2440/152260) while in subpopulation SAS AF = 0.0311 (150/4816). AF 95% confidence interval is 0.0271. There are 30 homozygotes in GnomAd4. There are 1258 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-450-30838G>A		intron_variant	Intron 1 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-374-117541G>A		intron_variant	Intron 1 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-374-117541G>A		intron_variant	Intron 5 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-450-30838G>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.388-117541G>A		intron_variant	Intron 5 of 20	2

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2438 AN: 152142 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00365

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0160 AC: 2440 AN: 152260 Hom.: 30 Cov.: 32 AF XY: 0.0169 AC XY: 1258 AN XY: 74446

African (AFR) AF: 0.00364 AC: 151 AN: 41536

American (AMR) AF: 0.0112 AC: 171 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4816

European-Finnish (FIN) AF: 0.0352 AC: 374 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0215 AC: 1462 AN: 68034

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.0193 Hom.: 36

Bravo AF: 0.0134

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.46
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1325445; hg19: chr1-58467375;