1-58214938-G-T

Variant names:

• chr1-58214938-G-T
• rs1416343
• NM_001379462.1:c.-451+35302C>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.-451+35302C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,984 control chromosomes in the GnomAD database, including 3,142 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 0.19 (3142 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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.-451+35302C>A		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-375+35302C>A		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-452-64350C>A		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.310-64350C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29118 AN: 151866 Hom.: 3120 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.192 AC: 29166 AN: 151984 Hom.: 3142 Cov.: 32 AF XY: 0.201 AC XY: 14935 AN XY: 74290

African (AFR) AF: 0.171 AC: 7104 AN: 41480

American (AMR) AF: 0.144 AC: 2200 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3464

East Asian (EAS) AF: 0.451 AC: 2316 AN: 5134

South Asian (SAS) AF: 0.375 AC: 1803 AN: 4806

European-Finnish (FIN) AF: 0.276 AC: 2914 AN: 10542

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

European-Non Finnish (NFE) AF: 0.171 AC: 11621 AN: 67974

Other (OTH) AF: 0.185 AC: 388 AN: 2100

Alfa AF: 0.105 Hom.: 163

Bravo AF: 0.178

Asia WGS AF: 0.436 AC: 1518 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.9
DANN	Benign	0.78
PhyloP100		1.7
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: rs1416343; hg19: chr1-58680610;