8-98117279-G-T

Variant names:

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

Variant summary

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

The NM_001145860.2(POP1):​c.-114G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 626,700 control chromosomes in the GnomAD database, including 13,669 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 0.20 (3271 hom., cov: 33)
  • Exomes 𝑓: 0.20 (10398 hom.)
• Consequence: POP1 NM_001145860.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

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>T		upstream_gene	N/A	NP_001139332.1
	RIDA	NM_005836.3	MANE Select	c.-183C>A		upstream_gene	N/A	NP_005827.1
	POP1	NM_001145861.2		c.-54G>T		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>T		upstream_gene	N/A	ENSP00000385787.2
	RIDA	ENST00000254878.8	TSL:1 MANE Select	c.-183C>A		upstream_gene	N/A	ENSP00000254878.3
	POP1	ENST00000916453.1		c.-589G>T		upstream_gene	N/A	ENSP00000586512.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30633 AN: 152032 Hom.: 3256 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.203 AC: 96197 AN: 474552 Hom.: 10398 Cov.: 5 AF XY: 0.201 AC XY: 51152 AN XY: 253908

African (AFR) AF: 0.178 AC: 2314 AN: 12970

American (AMR) AF: 0.212 AC: 4304 AN: 20326

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1526 AN: 14020

East Asian (EAS) AF: 0.127 AC: 3892 AN: 30754

South Asian (SAS) AF: 0.198 AC: 9657 AN: 48826

European-Finnish (FIN) AF: 0.279 AC: 8307 AN: 29768

Middle Eastern (MID) AF: 0.0830 AC: 188 AN: 2266

European-Non Finnish (NFE) AF: 0.211 AC: 60912 AN: 288810

Other (OTH) AF: 0.190 AC: 5097 AN: 26812

GnomAD4 genome AF: 0.202 AC: 30672 AN: 152148 Hom.: 3271 Cov.: 33 AF XY: 0.204 AC XY: 15139 AN XY: 74378

African (AFR) AF: 0.181 AC: 7538 AN: 41534

American (AMR) AF: 0.196 AC: 3002 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.108 AC: 556 AN: 5168

South Asian (SAS) AF: 0.208 AC: 1001 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3123 AN: 10578

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14535 AN: 67968

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.201 Hom.: 14461

Bravo AF: 0.191

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		-1.1
PromoterAI		-0.083	Neutral
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV54704146;