rs12035887

Variant names:

• chr1-57003118-G-T
• rs12035887
• NM_001365792.1:c.*16-4990C>A

Variant summary

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

The NM_001365792.1(DAB1):​c.*16-4990C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,194 control chromosomes in the GnomAD database, including 1,539 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 0.12 (1539 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• 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)

LOC112267900 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.*16-4990C>A		intron_variant	Intron 14 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.*16-4990C>A		intron_variant	Intron 14 of 14	5	NM_001365792.1	ENSP00000360280.1
DAB1	ENST00000420954.6	c.*16-4990C>A		intron_variant	Intron 13 of 13	1		ENSP00000395296.2
DAB1	ENST00000414851.6	c.*16-4990C>A		intron_variant	Intron 13 of 13	5		ENSP00000387581.3
DAB1	ENST00000485760.5	n.2439-4990C>A		intron_variant	Intron 20 of 20	2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 152076 Hom.: 1531 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.120 AC: 18301 AN: 152194 Hom.: 1539 Cov.: 33 AF XY: 0.127 AC XY: 9465 AN XY: 74422

African (AFR) AF: 0.117 AC: 4842 AN: 41526

American (AMR) AF: 0.253 AC: 3864 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1727 AN: 5154

South Asian (SAS) AF: 0.160 AC: 773 AN: 4820

European-Finnish (FIN) AF: 0.133 AC: 1412 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5100 AN: 68022

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.101 Hom.: 871

Bravo AF: 0.132

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.36
PhyloP100		0.098
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: rs12035887; hg19: chr1-57468791;