rs1417983

Variant names:

• chr1-58426924-G-A
• rs1417983
• NM_001379461.1:c.-505+79136C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379461.1(DAB1):​c.-505+79136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,056 control chromosomes in the GnomAD database, including 25,430 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 0.57 (25430 hom., cov: 33)
• Consequence: DAB1 NM_001379461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• Publications: 2 publications found

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]

OMA1 (HGNC:29661): (OMA1 zinc metallopeptidase) Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379461.1	c.-505+79136C>T		intron_variant	Intron 3 of 20		NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMA1	ENST00000467509.5	n.288-11439C>T		intron_variant	Intron 3 of 3	5
DAB1	ENST00000485760.5	n.257+79136C>T		intron_variant	Intron 3 of 20	2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86375 AN: 151938 Hom.: 25408 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.568 AC: 86442 AN: 152056 Hom.: 25430 Cov.: 33 AF XY: 0.565 AC XY: 41953 AN XY: 74304

African (AFR) AF: 0.727 AC: 30184 AN: 41494

American (AMR) AF: 0.425 AC: 6482 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2098 AN: 5158

South Asian (SAS) AF: 0.448 AC: 2159 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5692 AN: 10552

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35854 AN: 67986

Other (OTH) AF: 0.543 AC: 1144 AN: 2106

Alfa AF: 0.564 Hom.: 3063

Bravo AF: 0.563

Asia WGS AF: 0.430 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		0.50

Splicing

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

Other links and lift over

dbSNP: rs1417983; hg19: chr1-58892596;