1-57447555-T-C

Variant names:

• chr1-57447555-T-C
• rs12033655
• NM_001379462.1:c.-136-156389A>G

Variant summary

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

The NM_001379462.1(DAB1):​c.-136-156389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,162 control chromosomes in the GnomAD database, including 9,133 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 0.34 (9133 hom., cov: 33)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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.-136-156389A>G		intron	N/A	NP_001366391.1
	DAB1	NM_021080.5		c.-136-156389A>G		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-136-156389A>G		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.626-156389A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51412 AN: 152042 Hom.: 9116 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.338 AC: 51456 AN: 152162 Hom.: 9133 Cov.: 33 AF XY: 0.347 AC XY: 25784 AN XY: 74392

African (AFR) AF: 0.270 AC: 11199 AN: 41518

American (AMR) AF: 0.469 AC: 7167 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2796 AN: 5166

South Asian (SAS) AF: 0.499 AC: 2402 AN: 4818

European-Finnish (FIN) AF: 0.363 AC: 3838 AN: 10586

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21884 AN: 68000

Other (OTH) AF: 0.345 AC: 728 AN: 2110

Alfa AF: 0.334 Hom.: 14804

Bravo AF: 0.342

Asia WGS AF: 0.509 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.74
PhyloP100		0.37
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: rs12033655; hg19: chr1-57913227;