rs1109896

Positions:

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

Variant summary

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

The ENST00000654217.1(ENSG00000286918):​n.153+412A>C variant causes a intron, non coding transcript 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: ENST00000654217.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422

Genes affected

(HGNC:):

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OMA1	NM_145243.5			upstream_gene_variant		ENST00000371226.8	NP_660286.1
DAB1	NM_001379461.1			upstream_gene_variant			NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000654217.1	n.153+412A>C		intron_variant, non_coding_transcript_variant
OMA1	ENST00000371226.8			upstream_gene_variant		1	NM_145243.5	ENSP00000360270	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.681

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.671

Alfa AF: 0.680 Hom.: 7553

Bravo AF: 0.633

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs1109896; hg19: chr1-59012404; COSMIC: COSV62256731; COSMIC: COSV62256731;