chr1-58437666-A-G

Variant names:

• chr1-58437666-A-G
• rs706430
• XR_001738073.2:n.12360T>C

Variant summary

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

The XR_001738073.2(LOC107984960):​n.12360T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,160 control chromosomes in the GnomAD database, including 26,816 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 0.59 (26816 hom., cov: 34)
• Consequence: LOC107984960 XR_001738073.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 3 publications found

Genes affected

LOC107984960 (HGNC:):

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107984960	XR_001738073.2	n.12360T>C		non_coding_transcript_exon_variant	Exon 2 of 2
LOC107984960	XR_001738074.2	n.8522T>C		non_coding_transcript_exon_variant	Exon 3 of 3
LOC107984960	XR_001738075.2	n.12131T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMA1	ENST00000467509.5	n.288-22181T>C		intron_variant	Intron 3 of 3	5
DAB1	ENST00000485760.5	n.257+68394T>C		intron_variant	Intron 3 of 20	2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89196 AN: 152042 Hom.: 26795 Cov.: 34

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 89251 AN: 152160 Hom.: 26816 Cov.: 34 AF XY: 0.582 AC XY: 43285 AN XY: 74368

African (AFR) AF: 0.713 AC: 29597 AN: 41522

American (AMR) AF: 0.438 AC: 6697 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2070 AN: 5184

South Asian (SAS) AF: 0.496 AC: 2394 AN: 4824

European-Finnish (FIN) AF: 0.547 AC: 5783 AN: 10576

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38706 AN: 67992

Other (OTH) AF: 0.563 AC: 1182 AN: 2100

Alfa AF: 0.570 Hom.: 4460

Bravo AF: 0.578

Asia WGS AF: 0.463 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.69
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs706430; hg19: chr1-58903338;