rs1503646

Positions:

• chr1-58502270-T-C

Variant summary

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

The NM_145243.5(OMA1):​c.1365+3790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 152,322 control chromosomes in the GnomAD database, including 470 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 0.076 (470 hom., cov: 32)
• Consequence: OMA1 NM_145243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

Genes affected

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]

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5	c.1365+3790A>G		intron_variant		ENST00000371226.8
DAB1	NM_001379461.1	c.-505+3790A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8	c.1365+3790A>G		intron_variant		1	NM_145243.5	P1

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11501 AN: 152204 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0874

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

GnomAD4 genome AF: 0.0756 AC: 11510 AN: 152322 Hom.: 470 Cov.: 32 AF XY: 0.0727 AC XY: 5415 AN XY: 74484

Gnomad4 AFR AF: 0.0508

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.0865

Alfa AF: 0.0848 Hom.: 70

Bravo AF: 0.0742

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.50

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: rs1503646; hg19: chr1-58967942;