8-98123559-A-G

Position:

• chr8-98123559-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145860.2(POP1):​c.142+80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,343,110 control chromosomes in the GnomAD database, including 29,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2711 hom., cov: 32)
  • Exomes 𝑓: 0.21 (26523 hom.)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-98123559-A-G is Benign according to our data. Variant chr8-98123559-A-G is described in ClinVar as [Benign]. Clinvar id is 1257824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.142+80A>G		intron_variant		ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2	c.142+80A>G		intron_variant			NP_001139333.1
POP1	NM_015029.3	c.142+80A>G		intron_variant			NP_055844.2
POP1	XM_011516801.3	c.142+80A>G		intron_variant			XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7	c.142+80A>G		intron_variant		2	NM_001145860.2	ENSP00000385787	P1
POP1	ENST00000349693.3	c.142+80A>G		intron_variant		1		ENSP00000339529	P1
POP1	ENST00000522319.5	c.142+80A>G		intron_variant		4		ENSP00000428945

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27188 AN: 151996 Hom.: 2698 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.207 AC: 246292 AN: 1190996 Hom.: 26523 AF XY: 0.205 AC XY: 122877 AN XY: 599612

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.179 AC: 27224 AN: 152114 Hom.: 2711 Cov.: 32 AF XY: 0.181 AC XY: 13441 AN XY: 74342

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0855 Hom.: 165

Bravo AF: 0.167

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs28556674; hg19: chr8-99135787;