rs3861824

Variant names:

• chr1-58341545-G-A
• rs3861824
• NM_001379461.1:c.-453+1807C>T

Variant summary

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

The NM_001379461.1(DAB1):​c.-453+1807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,142 control chromosomes in the GnomAD database, including 1,241 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 0.13 (1241 hom., cov: 32)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-453+1807C>T		intron_variant	Intron 4 of 20		NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.309+1807C>T		intron_variant	Intron 4 of 20	2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19008 AN: 152024 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.125 AC: 19026 AN: 152142 Hom.: 1241 Cov.: 32 AF XY: 0.125 AC XY: 9310 AN XY: 74382

African (AFR) AF: 0.121 AC: 5016 AN: 41512

American (AMR) AF: 0.122 AC: 1866 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5180

South Asian (SAS) AF: 0.111 AC: 537 AN: 4818

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9285 AN: 67992

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.127 Hom.: 1009

Bravo AF: 0.120

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.44
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs3861824; hg19: chr1-58807217;