rs11810899

Variant names:

• chr1-57015611-T-C
• rs11810899
• NM_001365792.1:c.896-180A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365792.1(DAB1):​c.896-180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,216 control chromosomes in the GnomAD database, including 1,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1846 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.924
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-57015611-T-C is Benign according to our data. Variant chr1-57015611-T-C is described in ClinVar as [Benign]. Clinvar id is 1180157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.896-180A>G		intron_variant	Intron 11 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.896-180A>G		intron_variant	Intron 11 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20470 AN: 152098 Hom.: 1837 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.135 AC: 20501 AN: 152216 Hom.: 1846 Cov.: 33 AF XY: 0.142 AC XY: 10542 AN XY: 74410

African (AFR) AF: 0.163 AC: 6769 AN: 41548

American (AMR) AF: 0.258 AC: 3943 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1697 AN: 5150

South Asian (SAS) AF: 0.201 AC: 971 AN: 4830

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5104 AN: 68020

Other (OTH) AF: 0.121 AC: 256 AN: 2116

Alfa AF: 0.127 Hom.: 884

Bravo AF: 0.147

Asia WGS AF: 0.275 AC: 952 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11810899; hg19: chr1-57481284;