rs338901

Positions:

• chr1-58412598-G-A

Variant summary

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

The NM_001379461.1(DAB1):​c.-504-69195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,114 control chromosomes in the GnomAD database, including 33,238 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 0.64 (33238 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-504-69195C>T		intron_variant			NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.258-69195C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97888 AN: 151996 Hom.: 33197 Cov.: 33

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.644 AC: 97977 AN: 152114 Hom.: 33238 Cov.: 33 AF XY: 0.637 AC XY: 47361 AN XY: 74360

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.621

Alfa AF: 0.595 Hom.: 35770

Bravo AF: 0.642

Asia WGS AF: 0.487 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs338901; hg19: chr1-58878270;