rs3738556

Positions:

• chr1-57069525-C-A
• chr1-57069525-C-G
• chr1-57069525-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365792.1(DAB1):​c.598-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 954,090 control chromosomes in the GnomAD database, including 25,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4291 hom., cov: 32)
  • Exomes 𝑓: 0.21 (20989 hom.)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-57069525-C-A is Benign according to our data. Variant chr1-57069525-C-A is described in ClinVar as [Benign]. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.598-100G>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.598-100G>T		intron_variant		5	NM_001365792.1	ENSP00000360280	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33897 AN: 151910 Hom.: 4290 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.209 AC: 167366 AN: 802062 Hom.: 20989 AF XY: 0.208 AC XY: 87789 AN XY: 422218

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.223 AC: 33923 AN: 152028 Hom.: 4291 Cov.: 32 AF XY: 0.230 AC XY: 17052 AN XY: 74296

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.202

Alfa AF: 0.161 Hom.: 562

Bravo AF: 0.232

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.53
CADD	Benign	15
DANN	Benign	0.60

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: rs3738556; hg19: chr1-57535198;