rs11997551

chr8-98123209-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145860.2(POP1):c.-2-127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,090,134 control chromosomes in the GnomAD database, including 104,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14570 hom., cov: 33)
  • Exomes 𝑓: 0.43 (89763 hom.)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.964

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-98123209-A-G is Benign according to our data. Variant chr8-98123209-A-G is described in ClinVar as [Benign]. Clinvar id is 1230258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POP1	NM_001145860.2	c.-2-127A>G		intron_variant		ENST00000401707.7
POP1	NM_001145861.2	c.-2-127A>G		intron_variant
POP1	NM_015029.3	c.-2-127A>G		intron_variant
POP1	XM_011516801.3	c.-2-127A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POP1	ENST00000401707.7	c.-2-127A>G		intron_variant		2	NM_001145860.2	P1
POP1	ENST00000349693.3	c.-2-127A>G		intron_variant		1		P1
POP1	ENST00000522319.5	c.-2-127A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65875 AN: 151980 Hom.: 14560 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.433 AC: 406199 AN: 938036 Hom.: 89763 AF XY: 0.438 AC XY: 209619 AN XY: 478376

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.433 AC: 65911 AN: 152098 Hom.: 14570 Cov.: 33 AF XY: 0.434 AC XY: 32243 AN XY: 74358

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.443

Alfa AF: 0.427 Hom.: 2813

Bravo AF: 0.430

Asia WGS AF: 0.385 AC: 1339 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.66

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: rs11997551; hg19: chr8-99135437;