1-57014751-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365792.1(DAB1):c.1444+132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 626,808 control chromosomes in the GnomAD database, including 17,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7861 hom., cov: 33)
  • Exomes 𝑓: 0.17 (9374 hom.)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-57014751-C-G is Benign according to our data. Variant chr1-57014751-C-G is described in ClinVar as [Benign]. Clinvar id is 1235828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.1444+132G>C		intron_variant		ENST00000371236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.1444+132G>C		intron_variant		5	NM_001365792.1	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40620 AN: 151904 Hom.: 7809 Cov.: 33

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.166 AC: 78738 AN: 474786 Hom.: 9374 AF XY: 0.165 AC XY: 39910 AN XY: 241338

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.268 AC: 40738 AN: 152022 Hom.: 7861 Cov.: 33 AF XY: 0.272 AC XY: 20217 AN XY: 74308

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.234

Alfa AF: 0.203 Hom.: 613

Bravo AF: 0.288

Asia WGS AF: 0.331 AC: 1147 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 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.092
Dann	Benign	0.34

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: rs944923; hg19: chr1-57480424;