NM_001379462.1:c.-211+47569G>A

Variant names:

• chr1-57836430-C-T
• rs852787
• NM_001379462.1:c.-211+47569G>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.-211+47569G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,214 control chromosomes in the GnomAD database, including 2,397 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 0.16 (2397 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-211+47569G>A		intron_variant	Intron 3 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-211+47569G>A		intron_variant	Intron 2 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-211+47569G>A		intron_variant	Intron 6 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-211+47569G>A		intron_variant	Intron 3 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000477280.1	n.88-9975G>A		intron_variant	Intron 1 of 1	3
DAB1	ENST00000485760.5	n.551+47569G>A		intron_variant	Intron 6 of 20	2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24468 AN: 152096 Hom.: 2394 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.161 AC: 24479 AN: 152214 Hom.: 2397 Cov.: 32 AF XY: 0.161 AC XY: 11983 AN XY: 74406

African (AFR) AF: 0.0509 AC: 2117 AN: 41564

American (AMR) AF: 0.202 AC: 3092 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.0879 AC: 453 AN: 5156

South Asian (SAS) AF: 0.121 AC: 585 AN: 4826

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14461 AN: 68008

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.198 Hom.: 5445

Bravo AF: 0.157

Asia WGS AF: 0.103 AC: 360 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	0.61
DANN	Benign	0.51
PhyloP100		-0.75
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: rs852787; hg19: chr1-58302102;