1-57102332-G-C

Variant names:

• chr1-57102332-G-C
• rs3768176
• NM_001365792.1:c.307-29918C>G

Variant summary

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

The NM_001365792.1(DAB1):​c.307-29918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,032 control chromosomes in the GnomAD database, including 3,086 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 0.18 (3086 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• 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)

ENSG00000306020 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.307-29918C>G		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.307-29918C>G		intron_variant	Intron 4 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27508 AN: 151914 Hom.: 3083 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.181 AC: 27520 AN: 152032 Hom.: 3086 Cov.: 33 AF XY: 0.190 AC XY: 14123 AN XY: 74286

African (AFR) AF: 0.168 AC: 6963 AN: 41508

American (AMR) AF: 0.294 AC: 4488 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2847 AN: 5124

South Asian (SAS) AF: 0.266 AC: 1280 AN: 4814

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8922 AN: 67992

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.0743 Hom.: 97

Bravo AF: 0.188

Asia WGS AF: 0.379 AC: 1316 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.72
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: rs3768176; hg19: chr1-57568005;