chr1-57663964-G-A

Variant names:

• chr1-57663964-G-A
• rs4244011
• NM_001379462.1:c.-210-14299C>T

Variant summary

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

The NM_001379462.1(DAB1):​c.-210-14299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,008 control chromosomes in the GnomAD database, including 8,609 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 0.33 (8609 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001379462.1		c.-210-14299C>T		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-210-14299C>T		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-210-14299C>T		intron	N/A	NP_001366390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000485760.5	TSL:2	n.552-14299C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50126 AN: 151890 Hom.: 8603 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.330 AC: 50144 AN: 152008 Hom.: 8609 Cov.: 32 AF XY: 0.322 AC XY: 23921 AN XY: 74288

African (AFR) AF: 0.324 AC: 13419 AN: 41470

American (AMR) AF: 0.295 AC: 4511 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1334 AN: 3470

East Asian (EAS) AF: 0.0863 AC: 446 AN: 5168

South Asian (SAS) AF: 0.161 AC: 778 AN: 4820

European-Finnish (FIN) AF: 0.289 AC: 3043 AN: 10538

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25565 AN: 67958

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.365 Hom.: 13764

Bravo AF: 0.333

Asia WGS AF: 0.166 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		0.40
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: rs4244011; hg19: chr1-58129636;