chr1-57002262-A-G

Position:

• chr1-57002262-A-G

Variant summary

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

The NM_001365792.1(DAB1):​c.*16-4134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,218 control chromosomes in the GnomAD database, including 2,281 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 0.15 (2281 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.*16-4134T>C		intron_variant		ENST00000371236.7
LOC112267900	XR_007066117.1	n.2930A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.*16-4134T>C		intron_variant		5	NM_001365792.1	P1
DAB1	ENST00000420954.6	c.*16-4134T>C		intron_variant		1
DAB1	ENST00000414851.6	c.*16-4134T>C		intron_variant		5		P1
DAB1	ENST00000485760.5	n.2439-4134T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22838 AN: 152100 Hom.: 2272 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.150 AC: 22879 AN: 152218 Hom.: 2281 Cov.: 33 AF XY: 0.157 AC XY: 11671 AN XY: 74412

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.138

Alfa AF: 0.104 Hom.: 1306

Bravo AF: 0.165

Asia WGS AF: 0.257 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.83

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: rs11206955; hg19: chr1-57467935;