rs3131729

Variant names:

• chr1-57733095-C-T
• rs3131729
• NM_001379462.1:c.-210-83430G>A

Variant summary

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

The NM_001379462.1(DAB1):​c.-210-83430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,684 control chromosomes in the GnomAD database, including 3,748 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 0.20 (3748 hom., cov: 31)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 1 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)

ENSG00000293827 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-210-83430G>A		intron_variant	Intron 3 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-210-83430G>A		intron_variant	Intron 2 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-210-83430G>A		intron_variant	Intron 6 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-210-83430G>A		intron_variant	Intron 3 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.552-83430G>A		intron_variant	Intron 6 of 20	2
ENSG00000293827	ENST00000719271.1	n.104+9025C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29767 AN: 151566 Hom.: 3744 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.196 AC: 29802 AN: 151684 Hom.: 3748 Cov.: 31 AF XY: 0.195 AC XY: 14456 AN XY: 74100

African (AFR) AF: 0.332 AC: 13693 AN: 41284

American (AMR) AF: 0.143 AC: 2183 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2076 AN: 5124

South Asian (SAS) AF: 0.213 AC: 1016 AN: 4780

European-Finnish (FIN) AF: 0.112 AC: 1182 AN: 10528

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8909 AN: 67940

Other (OTH) AF: 0.164 AC: 346 AN: 2112

Alfa AF: 0.151 Hom.: 1279

Bravo AF: 0.206

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3131729; hg19: chr1-58198767;