rs12128305

Variant names:

• chr1-57321846-T-A
• rs12128305
• NM_001365792.1:c.-136-30680A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001365792.1(DAB1):​c.-136-30680A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,020 control chromosomes in the GnomAD database, including 5,782 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 0.24 (5782 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.-136-30680A>T		intron_variant	Intron 1 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.-136-30680A>T		intron_variant	Intron 1 of 14	5	NM_001365792.1	ENSP00000360280.1
DAB1	ENST00000371230.1	c.-136-30680A>T		intron_variant	Intron 1 of 6	5		ENSP00000360274.1
DAB1	ENST00000485760.5	n.626-30680A>T		intron_variant	Intron 7 of 20	2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37194 AN: 151902 Hom.: 5781 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.245 AC: 37194 AN: 152020 Hom.: 5782 Cov.: 32 AF XY: 0.238 AC XY: 17705 AN XY: 74288

African (AFR) AF: 0.0730 AC: 3028 AN: 41478

American (AMR) AF: 0.224 AC: 3417 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3468

East Asian (EAS) AF: 0.103 AC: 532 AN: 5172

South Asian (SAS) AF: 0.150 AC: 724 AN: 4818

European-Finnish (FIN) AF: 0.282 AC: 2967 AN: 10536

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24138 AN: 67964

Other (OTH) AF: 0.272 AC: 574 AN: 2110

Alfa AF: 0.302 Hom.: 938

Bravo AF: 0.236

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.3
DANN	Benign	0.75
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12128305; hg19: chr1-57787518; COSMIC: COSV64680391;