8-98117279-G-T

Position:

• chr8-98117279-G-T

Variant summary

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

The 8-98117279-G-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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POP1	NM_001145860.2			upstream_gene_variant		ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2			upstream_gene_variant			NP_001139333.1
POP1	XM_011516801.3			upstream_gene_variant			XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7			upstream_gene_variant		2	NM_001145860.2	ENSP00000385787	P1
POP1	ENST00000522319.5			upstream_gene_variant		4		ENSP00000428945

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

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.190

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

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.176

Alfa AF: 0.197 Hom.: 6788

Bravo AF: 0.191

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071598; hg19: chr8-99129507; COSMIC: COSV54704146;