rs7533282

Variant names:

• chr1-57167823-T-G
• rs7533282
• NM_001365792.1:c.68-22394A>C

Variant summary

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

The NM_001365792.1(DAB1):​c.68-22394A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,142 control chromosomes in the GnomAD database, including 4,190 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 0.18 (4190 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.68-22394A>C		intron	N/A	NP_001352721.1
	DAB1	NM_001353983.2		c.68-22394A>C		intron	N/A	NP_001340912.1
	DAB1	NM_001353985.2		c.68-22394A>C		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.68-22394A>C		intron	N/A	ENSP00000360280.1
	DAB1	ENST00000420954.6	TSL:1	c.68-22394A>C		intron	N/A	ENSP00000395296.2
	DAB1	ENST00000371231.5	TSL:5	c.68-22394A>C		intron	N/A	ENSP00000360275.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28048 AN: 152024 Hom.: 4172 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0537

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.185 AC: 28113 AN: 152142 Hom.: 4190 Cov.: 32 AF XY: 0.179 AC XY: 13312 AN XY: 74406

African (AFR) AF: 0.409 AC: 16949 AN: 41436

American (AMR) AF: 0.132 AC: 2017 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4822

European-Finnish (FIN) AF: 0.0412 AC: 438 AN: 10624

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7536 AN: 68010

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.133 Hom.: 3074

Bravo AF: 0.199

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.68
PhyloP100		1.3
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: rs7533282; hg19: chr1-57633496; COSMIC: COSV59724558;