rs2991515

chr1-57418638-G-Achr1-57418638-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365792.1(DAB1):c.-137+5292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,842 control chromosomes in the GnomAD database, including 16,435 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16435 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.-137+5292C>T		intron_variant		ENST00000371236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.-137+5292C>T		intron_variant		5	NM_001365792.1	P1
DAB1	ENST00000371230.1	c.-137+5292C>T		intron_variant		5
DAB1	ENST00000485760.5	n.626-127472C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69127 AN: 151724 Hom.: 16396 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.456 AC: 69214 AN: 151842 Hom.: 16435 Cov.: 32 AF XY: 0.443 AC XY: 32901 AN XY: 74218

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.458

Alfa AF: 0.450 Hom.: 21890

Bravo AF: 0.465

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	13
Dann	Benign	0.78

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: rs2991515; hg19: chr1-57884310; COSMIC: COSV64680903;