dbSNP rs1109896: OMA1:c.-134T>G (chr1-58546732-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000906297.1(OMA1):c.-134T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,124 control chromosomes in the GnomAD database, including 34,186 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 0.65 ( 34128 hom., cov: 31)

Exomes 𝑓: 0.70 ( 58 hom. )

Consequence

OMA1
ENST00000906297.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.422

Publications

14 publications found

Variant links:

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]

OMA1 links:

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)

DAB1 links:

ENSG00000286918 (HGNC:):

ENSG00000286918 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000906297.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMA1	NM_145243.5	MANE Select	c.-46T>G		upstream_gene	N/A	NP_660286.1	Q96E52-1
	DAB1	NM_001379461.1		c.-759T>G		upstream_gene	N/A	NP_001366390.1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
OMA1	ENST00000906297.1	c.-134T>G	5_prime_UTR	Exon 1 of 10	ENSP00000576356.1
OMA1	ENST00000929571.1	c.-161T>G	5_prime_UTR	Exon 1 of 10	ENSP00000599630.1
OMA1	ENST00000929572.1	c.-269T>G	5_prime_UTR	Exon 1 of 10	ENSP00000599631.1

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98598

AN:

151784

Hom.:

34115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.714

Gnomad EAS

AF:

0.945

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.667

GnomAD4 exome

AF:

0.703

AC:

156

AN:

222

Hom.:

Cov.:

AF XY:

0.728

AC XY:

131

AN XY:

180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.681

AC:

128

AN:

188

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.649

AC:

98633

AN:

151902

Hom.:

34128

Cov.:

AF XY:

0.662

AC XY:

49137

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.392

AC:

16214

AN:

41374

American (AMR)

AF:

0.753

AC:

11500

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

2477

AN:

3470

East Asian (EAS)

AF:

0.945

AC:

4845

AN:

5128

South Asian (SAS)

AF:

0.803

AC:

3864

AN:

4810

European-Finnish (FIN)

AF:

0.820

AC:

8669

AN:

10578

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48951

AN:

67946

Other (OTH)

AF:

0.671

AC:

1417

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.668

Hom.:

8374

Bravo

AF:

0.633

Asia WGS

AF:

0.841

AC:

2924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.6

(source)

DANN

Benign

0.82

PhyloP100

-0.42

PromoterAI

0.070

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over