rs1394397

Variant names:

• chr1-57190938-A-G
• rs1394397
• NM_001365792.1:c.68-45509T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-57190938-A-G
• chr1-57190938-A-T

Variant summary

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

The NM_001365792.1(DAB1):​c.68-45509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,318 control chromosomes in the GnomAD database, including 241 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 0.046 (241 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.68-45509T>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.68-45509T>C		intron_variant	Intron 2 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6963 AN: 152200 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0458 AC: 6977 AN: 152318 Hom.: 241 Cov.: 32 AF XY: 0.0449 AC XY: 3347 AN XY: 74478

African (AFR) AF: 0.0990 AC: 4113 AN: 41554

American (AMR) AF: 0.0269 AC: 412 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4828

European-Finnish (FIN) AF: 0.0297 AC: 316 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1822 AN: 68034

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0354 Hom.: 44

Bravo AF: 0.0480

Asia WGS AF: 0.0170 AC: 60 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	13
DANN	Benign	0.73
PhyloP100		-0.028
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: rs1394397; hg19: chr1-57656611;