rs12043436

chr1-58540037-G-A

Variant summary

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

The NM_145243.5(OMA1):c.-16-727C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,954 control chromosomes in the GnomAD database, including 7,827 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 0.30 (7827 hom., cov: 30)
• Consequence: OMA1 NM_145243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5	c.-16-727C>T		intron_variant		ENST00000371226.8
DAB1	NM_001379461.1	c.-730+6666C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8	c.-16-727C>T		intron_variant		1	NM_145243.5	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45723 AN: 151836 Hom.: 7822 Cov.: 30

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.301 AC: 45724 AN: 151954 Hom.: 7827 Cov.: 30 AF XY: 0.305 AC XY: 22669 AN XY: 74270

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.332

Alfa AF: 0.354 Hom.: 4718

Bravo AF: 0.276

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.72
Dann	Benign	0.24

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: rs12043436; hg19: chr1-59005709;