chr1-58361374-C-A

Variant names:

• chr1-58361374-C-A
• rs1213659
• NM_001379461.1:c.-504-17971G>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.-504-17971G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,348 control chromosomes in the GnomAD database, including 64,620 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 0.92 (64620 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-504-17971G>T		intron_variant	Intron 3 of 20		NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.258-17971G>T		intron_variant	Intron 3 of 20	2

Frequencies

GnomAD3 genomes AF: 0.920 AC: 140024 AN: 152230 Hom.: 64566 Cov.: 33

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.920 AC: 140133 AN: 152348 Hom.: 64620 Cov.: 33 AF XY: 0.922 AC XY: 68706 AN XY: 74488

African (AFR) AF: 0.978 AC: 40672 AN: 41598

American (AMR) AF: 0.936 AC: 14325 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3062 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5182

South Asian (SAS) AF: 0.896 AC: 4328 AN: 4828

European-Finnish (FIN) AF: 0.910 AC: 9661 AN: 10620

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59883 AN: 68026

Other (OTH) AF: 0.913 AC: 1929 AN: 2112

Alfa AF: 0.911 Hom.: 17157

Bravo AF: 0.925

Asia WGS AF: 0.934 AC: 3247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		0.99

Splicing

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

Other links and lift over

dbSNP: rs1213659; hg19: chr1-58827046;