rs1924267

Variant names:

• chr1-57782100-C-T
• rs1924267
• NM_001379462.1:c.-211+101899G>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.-211+101899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,108 control chromosomes in the GnomAD database, including 1,854 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 0.15 (1854 hom., cov: 33)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-211+101899G>A		intron_variant	Intron 3 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-211+101899G>A		intron_variant	Intron 2 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-211+101899G>A		intron_variant	Intron 6 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-211+101899G>A		intron_variant	Intron 3 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.551+101899G>A		intron_variant	Intron 6 of 20	2

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22356 AN: 151990 Hom.: 1846 Cov.: 33

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.147 AC: 22388 AN: 152108 Hom.: 1854 Cov.: 33 AF XY: 0.146 AC XY: 10867 AN XY: 74364

African (AFR) AF: 0.0811 AC: 3369 AN: 41524

American (AMR) AF: 0.136 AC: 2074 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1318 AN: 5170

South Asian (SAS) AF: 0.149 AC: 718 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1497 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12163 AN: 67952

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.170 Hom.: 6571

Bravo AF: 0.144

Asia WGS AF: 0.196 AC: 680 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.26
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: rs1924267; hg19: chr1-58247772;