rs12035887

chr1-57003118-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.*16-4990C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,194 control chromosomes in the GnomAD database, including 1,539 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 0.12 (1539 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.*16-4990C>A		intron_variant		ENST00000371236.7
LOC112267900	XR_007066117.1	n.3786G>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.*16-4990C>A		intron_variant		5	NM_001365792.1	P1
DAB1	ENST00000420954.6	c.*16-4990C>A		intron_variant		1
DAB1	ENST00000414851.6	c.*16-4990C>A		intron_variant		5		P1
DAB1	ENST00000485760.5	n.2439-4990C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 152076 Hom.: 1531 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.120 AC: 18301 AN: 152194 Hom.: 1539 Cov.: 33 AF XY: 0.127 AC XY: 9465 AN XY: 74422

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0977 Hom.: 565

Bravo AF: 0.132

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.91
Dann	Benign	0.36

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: rs12035887; hg19: chr1-57468791;