NM_001365792.1:c.68-14830A>G

Variant names:

• chr1-57160259-T-C
• rs17541203
• NM_001365792.1:c.68-14830A>G

Variant summary

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

The NM_001365792.1(DAB1):​c.68-14830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,284 control chromosomes in the GnomAD database, including 371 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 0.056 (371 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. 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_001365792.1	MANE Select	c.68-14830A>G		intron	N/A	NP_001352721.1
	DAB1	NM_001353983.2		c.68-14830A>G		intron	N/A	NP_001340912.1
	DAB1	NM_001353985.2		c.68-14830A>G		intron	N/A	NP_001340914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.68-14830A>G		intron	N/A	ENSP00000360280.1
	DAB1	ENST00000420954.6	TSL:1	c.68-14830A>G		intron	N/A	ENSP00000395296.2
	DAB1	ENST00000371231.5	TSL:5	c.68-14830A>G		intron	N/A	ENSP00000360275.1

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8465 AN: 152166 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0556 AC: 8470 AN: 152284 Hom.: 371 Cov.: 32 AF XY: 0.0603 AC XY: 4493 AN XY: 74454

African (AFR) AF: 0.0124 AC: 515 AN: 41566

American (AMR) AF: 0.0347 AC: 530 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.159 AC: 825 AN: 5174

South Asian (SAS) AF: 0.139 AC: 673 AN: 4830

European-Finnish (FIN) AF: 0.120 AC: 1272 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4331 AN: 68028

Other (OTH) AF: 0.0477 AC: 101 AN: 2116

Alfa AF: 0.0473 Hom.: 218

Bravo AF: 0.0442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.85
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17541203; hg19: chr1-57625932;