8-98127382-C-T

Position:

• chr8-98127382-C-T

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.143-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,994 control chromosomes in the GnomAD database, including 18,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18940 hom., cov: 31)
• Consequence: POP1 NM_001145860.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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=-0.82).
• BP6: Variant 8-98127382-C-T is Benign according to our data. Variant chr8-98127382-C-T is described in ClinVar as [Benign]. Clinvar id is 1267711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POP1	NM_001145860.2	c.143-213C>T		intron_variant		ENST00000401707.7	NP_001139332.1
POP1	NM_001145861.2	c.143-213C>T		intron_variant			NP_001139333.1
POP1	NM_015029.3	c.143-213C>T		intron_variant			NP_055844.2
POP1	XM_011516801.3	c.143-213C>T		intron_variant			XP_011515103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POP1	ENST00000401707.7	c.143-213C>T		intron_variant		2	NM_001145860.2	ENSP00000385787	P1
POP1	ENST00000349693.3	c.143-213C>T		intron_variant		1		ENSP00000339529	P1
POP1	ENST00000522319.5	c.143-213C>T		intron_variant		4		ENSP00000428945

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75073 AN: 151874 Hom.: 18930 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.494 AC: 75110 AN: 151994 Hom.: 18940 Cov.: 31 AF XY: 0.494 AC XY: 36688 AN XY: 74302

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.494

Alfa AF: 0.521 Hom.: 28311

Bravo AF: 0.481

Asia WGS AF: 0.395 AC: 1374 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	-0.82
CADD	Benign	6.2
DANN	Benign	0.82

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: rs4735529; hg19: chr8-99139610;