rs12043436

Variant names:

• chr1-58540037-G-A
• rs12043436
• NM_145243.5:c.-16-727C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

DAB1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 37

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OMA1	NM_145243.5	c.-16-727C>T		intron_variant	Intron 1 of 8	ENST00000371226.8	NP_660286.1
DAB1	NM_001379461.1	c.-730+6666C>T		intron_variant	Intron 1 of 20		NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMA1	ENST00000371226.8	c.-16-727C>T		intron_variant	Intron 1 of 8	1	NM_145243.5	ENSP00000360270.3

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

African (AFR) AF: 0.152 AC: 6291 AN: 41444

American (AMR) AF: 0.257 AC: 3928 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1278 AN: 5166

South Asian (SAS) AF: 0.338 AC: 1624 AN: 4810

European-Finnish (FIN) AF: 0.450 AC: 4742 AN: 10534

Middle Eastern (MID) AF: 0.337 AC: 97 AN: 288

European-Non Finnish (NFE) AF: 0.374 AC: 25404 AN: 67956

Other (OTH) AF: 0.332 AC: 699 AN: 2104

Alfa AF: 0.353 Hom.: 5209

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
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12043436; hg19: chr1-59005709;