8-98117279-G-C

Variant names:

• chr8-98117279-G-C
• rs2071598
• NM_001145860.2:c.-114G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145860.2(POP1):​c.-114G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: POP1 NM_001145860.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

POP1 (HGNC:30129): (POP1 homolog, ribonuclease P/MRP subunit) This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

RIDA (HGNC:16897): (reactive intermediate imine deaminase A homolog) Enables 2-iminobutanoate deaminase activity and mRNA binding activity. Involved in mRNA catabolic process; mRNA destabilization; and organonitrogen compound catabolic process. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145860.2. 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
	POP1	NM_001145860.2	MANE Select	c.-114G>C		upstream_gene	N/A	NP_001139332.1
	RIDA	NM_005836.3	MANE Select	c.-183C>G		upstream_gene	N/A	NP_005827.1
	POP1	NM_001145861.2		c.-54G>C		upstream_gene	N/A	NP_001139333.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POP1	ENST00000401707.7	TSL:2 MANE Select	c.-114G>C		upstream_gene	N/A	ENSP00000385787.2
	RIDA	ENST00000254878.8	TSL:1 MANE Select	c.-183C>G		upstream_gene	N/A	ENSP00000254878.3
	POP1	ENST00000916453.1		c.-589G>C		upstream_gene	N/A	ENSP00000586512.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.73
PhyloP100		-1.1
PromoterAI		-0.098	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2071598; hg19: chr8-99129507;