rs17450764

Variant names:

• chr1-57011477-G-A
• rs17450764
• NM_001365792.1:c.1445-205C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001365792.1(DAB1):​c.1445-205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 152,240 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (74 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365
• Publications: 0 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)

LOC112267900 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-57011477-G-A is Benign according to our data. Variant chr1-57011477-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0278 (4227/152240) while in subpopulation SAS AF = 0.0444 (214/4818). AF 95% confidence interval is 0.0395. There are 74 homozygotes in GnomAd4. There are 2166 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4227 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001365792.1	MANE Select	c.1445-205C>T		intron	N/A	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1445-205C>T		intron	N/A	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1445-205C>T		intron	N/A	NP_001340914.1	O75553-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.1445-205C>T		intron	N/A	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1439-205C>T		intron	N/A	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1544-205C>T		intron	N/A	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4224 AN: 152122 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.00710

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0278 AC: 4227 AN: 152240 Hom.: 74 Cov.: 33 AF XY: 0.0291 AC XY: 2166 AN XY: 74448

African (AFR) AF: 0.00710 AC: 295 AN: 41540

American (AMR) AF: 0.0227 AC: 347 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4818

European-Finnish (FIN) AF: 0.0624 AC: 662 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0369 AC: 2510 AN: 68008

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0316 Hom.: 5

Bravo AF: 0.0222

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.56
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism

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: rs17450764; hg19: chr1-57477150; COSMIC: COSV64698039; COSMIC: COSV64698039;