1-57180988-T-G

Variant names:

• chr1-57180988-T-G
• rs9970802
• NM_001365792.1:c.68-35559A>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.68-35559A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,998 control chromosomes in the GnomAD database, including 27,843 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 0.60 (27843 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 4 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)

ENSG00000301670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.68-35559A>C		intron_variant	Intron 2 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.68-35559A>C		intron_variant	Intron 2 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90868 AN: 151880 Hom.: 27811 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.598 AC: 90954 AN: 151998 Hom.: 27843 Cov.: 32 AF XY: 0.589 AC XY: 43788 AN XY: 74284

African (AFR) AF: 0.724 AC: 30001 AN: 41440

American (AMR) AF: 0.464 AC: 7087 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2060 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2816 AN: 5152

South Asian (SAS) AF: 0.541 AC: 2604 AN: 4816

European-Finnish (FIN) AF: 0.500 AC: 5276 AN: 10548

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39060 AN: 67974

Other (OTH) AF: 0.607 AC: 1281 AN: 2112

Alfa AF: 0.583 Hom.: 85745

Bravo AF: 0.600

Asia WGS AF: 0.529 AC: 1844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.48
PhyloP100		-1.6
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: rs9970802; hg19: chr1-57646661;