chr1-57011477-G-A

Position:

• chr1-57011477-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC112267900 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4227 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.1445-205C>T		intron_variant		ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.1445-205C>T		intron_variant		5	NM_001365792.1	ENSP00000360280.1

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

Gnomad4 AFR AF: 0.00710

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0316 Hom.: 5

Bravo AF: 0.0222

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

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