rs1109896

Variant names:

• chr1-58546732-A-C
• rs1109896
• ENST00000906297.1:c.-134T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-58546732-A-C
• chr1-58546732-A-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 14 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)

ENSG00000286918 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 31

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.: 58 Cov.: 0 AF XY: 0.728 AC XY: 131 AN XY: 180

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 1.00 AC: 10 AN: 10

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.700 AC: 7 AN: 10

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.681 AC: 128 AN: 188

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.649 AC: 98633 AN: 151902 Hom.: 34128 Cov.: 31 AF XY: 0.662 AC XY: 49137 AN XY: 74256

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

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
DANN	Benign	0.82
PhyloP100		-0.42
PromoterAI		0.070	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1109896;

hg19: chr1-59012404;

COSMIC: COSV62256731;

COSMIC: COSV62256731;