rs1202773

chr1-57938951-G-A

Variant summary

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

The NM_021080.5(DAB1):c.-374-54789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,786 control chromosomes in the GnomAD database, including 3,146 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 0.17 (3146 hom., cov: 31)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001353980.2	c.-375+31839C>T		intron_variant
DAB1	NM_001379461.1	c.-374-54789C>T		intron_variant
DAB1	NM_001379462.1	c.-375+31839C>T		intron_variant
DAB1	NM_021080.5	c.-374-54789C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000485760.5	n.388-54789C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25123 AN: 151668 Hom.: 3139 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.166 AC: 25173 AN: 151786 Hom.: 3146 Cov.: 31 AF XY: 0.165 AC XY: 12241 AN XY: 74156

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.130

Alfa AF: 0.122 Hom.: 401

Bravo AF: 0.169

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.73
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1202773; hg19: chr1-58404623;