1-57010704-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001365792.1(DAB1):c.1659C>T(p.Ala553=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,573,906 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (39 hom.)
• Consequence: DAB1 NM_001365792.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.04

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-57010704-G-A is Benign according to our data. Variant chr1-57010704-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 780002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.04 with no splicing effect.
• BS2: High AC in GnomAd at 720 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.1659C>T	p.Ala553=	synonymous_variant	14/15	ENST00000371236.7
LOC112267900	XR_007066117.1	n.11372G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.1659C>T	p.Ala553=	synonymous_variant	14/15	5	NM_001365792.1	P1

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 720 AN: 152088 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00546 AC: 1296 AN: 237194 Hom.: 9 AF XY: 0.00548 AC XY: 704 AN XY: 128378

Gnomad AFR exome AF: 0.000965

Gnomad AMR exome AF: 0.00549

Gnomad ASJ exome AF: 0.0299

Gnomad EAS exome AF: 0.0000585

Gnomad SAS exome AF: 0.00258

Gnomad FIN exome AF: 0.000516

Gnomad NFE exome AF: 0.00650

Gnomad OTH exome AF: 0.00703

GnomAD4 exome AF: 0.00561 AC: 7975 AN: 1421700 Hom.: 39 Cov.: 30 AF XY: 0.00561 AC XY: 3946 AN XY: 703920

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00647

Gnomad4 ASJ exome AF: 0.0289

Gnomad4 EAS exome AF: 0.0000777

Gnomad4 SAS exome AF: 0.00229

Gnomad4 FIN exome AF: 0.000704

Gnomad4 NFE exome AF: 0.00579

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.00472 AC: 719 AN: 152206 Hom.: 4 Cov.: 32 AF XY: 0.00446 AC XY: 332 AN XY: 74416

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00615

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00629

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00649 Hom.: 5

Bravo AF: 0.00541

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	DAB1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs141647150; hg19: chr1-57476377;