NM_001365792.1:c.67+13392T>A

Variant names:

• chr1-57277572-A-T
• rs694060
• NM_001365792.1:c.67+13392T>A

Variant summary

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

The NM_001365792.1(DAB1):​c.67+13392T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,006 control chromosomes in the GnomAD database, including 45,668 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 0.77 (45668 hom., cov: 31)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 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.67+13392T>A		intron	N/A	NP_001352721.1
	DAB1	NM_001353983.2		c.67+13392T>A		intron	N/A	NP_001340912.1
	DAB1	NM_001353985.2		c.67+13392T>A		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.67+13392T>A		intron	N/A	ENSP00000360280.1
	DAB1	ENST00000420954.6	TSL:1	c.67+13392T>A		intron	N/A	ENSP00000395296.2
	DAB1	ENST00000371231.5	TSL:5	c.67+13392T>A		intron	N/A	ENSP00000360275.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116255 AN: 151888 Hom.: 45604 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.766 AC: 116376 AN: 152006 Hom.: 45668 Cov.: 31 AF XY: 0.767 AC XY: 56983 AN XY: 74278

African (AFR) AF: 0.941 AC: 39025 AN: 41480

American (AMR) AF: 0.839 AC: 12818 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2203 AN: 3462

East Asian (EAS) AF: 0.674 AC: 3469 AN: 5148

South Asian (SAS) AF: 0.681 AC: 3276 AN: 4808

European-Finnish (FIN) AF: 0.667 AC: 7035 AN: 10552

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46171 AN: 67968

Other (OTH) AF: 0.774 AC: 1636 AN: 2114

Alfa AF: 0.739 Hom.: 5256

Bravo AF: 0.787

Asia WGS AF: 0.673 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		-0.14
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: rs694060; hg19: chr1-57743244;