1-57085896-A-G

Variant names:

• chr1-57085896-A-G
• rs514412
• NM_001365792.1:c.307-13482T>C

Variant summary

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

The NM_001365792.1(DAB1):​c.307-13482T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,092 control chromosomes in the GnomAD database, including 43,116 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 0.75 (43116 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.307-13482T>C		intron_variant	Intron 4 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.307-13482T>C		intron_variant	Intron 4 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113922 AN: 151972 Hom.: 43073 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.750 AC: 114016 AN: 152092 Hom.: 43116 Cov.: 32 AF XY: 0.751 AC XY: 55835 AN XY: 74340

African (AFR) AF: 0.666 AC: 27615 AN: 41450

American (AMR) AF: 0.830 AC: 12693 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2694 AN: 3472

East Asian (EAS) AF: 0.935 AC: 4820 AN: 5154

South Asian (SAS) AF: 0.816 AC: 3931 AN: 4820

European-Finnish (FIN) AF: 0.708 AC: 7496 AN: 10582

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52150 AN: 68004

Other (OTH) AF: 0.774 AC: 1633 AN: 2110

Alfa AF: 0.772 Hom.: 78358

Bravo AF: 0.757

Asia WGS AF: 0.851 AC: 2958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.91
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: rs514412; hg19: chr1-57551569;