8-98123775-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145860.2(POP1):c.142+311dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 123,536 control chromosomes in the GnomAD database, including 3,946 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (3946 hom., cov: 21)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.193

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 -10 ACMG points.

• BP6: Variant 8-98123775-C-CA is Benign according to our data. Variant chr8-98123775-C-CA is described in ClinVar as [Benign]. Clinvar id is 1269370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POP1	NM_001145860.2	c.142+311dup		intron_variant		ENST00000401707.7
POP1	NM_001145861.2	c.142+311dup		intron_variant
POP1	NM_015029.3	c.142+311dup		intron_variant
POP1	XM_011516801.3	c.142+311dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POP1	ENST00000401707.7	c.142+311dup		intron_variant		2	NM_001145860.2	P1
POP1	ENST00000349693.3	c.142+311dup		intron_variant		1		P1
POP1	ENST00000522319.5	c.142+311dup		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.270 AC: 33413 AN: 123528 Hom.: 3939 Cov.: 21

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.271 AC: 33428 AN: 123536 Hom.: 3946 Cov.: 21 AF XY: 0.269 AC XY: 15928 AN XY: 59188

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.233

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs1274675081; hg19: chr8-99136003;