rs11997551

Variant names:

• chr8-98123209-A-G
• rs11997551
• NM_001145860.2:c.-2-127A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.964
• Publications: 1 publications found

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]

POP1 Gene-Disease associations (from GenCC):

• anauxetic dysplasia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• anauxetic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1230258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145860.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POP1	NM_001145860.2	MANE Select	c.-2-127A>G		intron	N/A	NP_001139332.1	Q99575
	POP1	NM_001145861.2		c.-2-127A>G		intron	N/A	NP_001139333.1	Q99575
	POP1	NM_015029.3		c.-2-127A>G		intron	N/A	NP_055844.2	Q99575

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POP1	ENST00000401707.7	TSL:2 MANE Select	c.-2-127A>G		intron	N/A	ENSP00000385787.2	Q99575
	POP1	ENST00000349693.3	TSL:1	c.-2-127A>G		intron	N/A	ENSP00000339529.3	Q99575
	POP1	ENST00000916453.1		c.-2-127A>G		intron	N/A	ENSP00000586512.1

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

African (AFR) AF: 0.439 AC: 9392 AN: 21374

American (AMR) AF: 0.422 AC: 12288 AN: 29122

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 10572 AN: 19968

East Asian (EAS) AF: 0.312 AC: 9915 AN: 31748

South Asian (SAS) AF: 0.541 AC: 35100 AN: 64930

European-Finnish (FIN) AF: 0.405 AC: 14396 AN: 35508

Middle Eastern (MID) AF: 0.598 AC: 1885 AN: 3154

European-Non Finnish (NFE) AF: 0.426 AC: 294288 AN: 690752

Other (OTH) AF: 0.443 AC: 18363 AN: 41480

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

African (AFR) AF: 0.442 AC: 18326 AN: 41470

American (AMR) AF: 0.444 AC: 6783 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1402 AN: 5178

South Asian (SAS) AF: 0.525 AC: 2536 AN: 4826

European-Finnish (FIN) AF: 0.386 AC: 4073 AN: 10556

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29414 AN: 67994

Other (OTH) AF: 0.443 AC: 935 AN: 2112

Alfa AF: 0.427 Hom.: 2813

Bravo AF: 0.430

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.66
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11997551; hg19: chr8-99135437;