rs1503646

Variant names:

• chr1-58502270-T-C
• rs1503646
• NM_145243.5:c.1365+3790A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145243.5. 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.1365+3790A>G		intron	N/A	NP_660286.1	Q96E52-1
	DAB1	NM_001379461.1		c.-505+3790A>G		intron	N/A	NP_001366390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OMA1	ENST00000371226.8	TSL:1 MANE Select	c.1365+3790A>G		intron	N/A	ENSP00000360270.3	Q96E52-1
	OMA1	ENST00000906297.1		c.1365+3790A>G		intron	N/A	ENSP00000576356.1
	OMA1	ENST00000906298.1		c.1365+3790A>G		intron	N/A	ENSP00000576357.1

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

African (AFR) AF: 0.0508 AC: 2111 AN: 41570

American (AMR) AF: 0.0679 AC: 1039 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.0526 AC: 254 AN: 4830

European-Finnish (FIN) AF: 0.0706 AC: 749 AN: 10616

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6669 AN: 68030

Other (OTH) AF: 0.0865 AC: 183 AN: 2116

Alfa AF: 0.0839 Hom.: 73

Bravo AF: 0.0742

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		0.042
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: rs1503646; hg19: chr1-58967942;