8-98123775-CAAA-CAAAA

Variant names:

• chr8-98123775-C-CA
• rs1274675081
• NM_001145860.2:c.142+311dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145860.2(POP1):​c.142+311dupA 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
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae)
• anauxetic dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.142+311dupA		intron	N/A	NP_001139332.1	Q99575
	POP1	NM_001145861.2		c.142+311dupA		intron	N/A	NP_001139333.1	Q99575
	POP1	NM_015029.3		c.142+311dupA		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.142+296_142+297insA		intron	N/A	ENSP00000385787.2	Q99575
	POP1	ENST00000349693.3	TSL:1	c.142+296_142+297insA		intron	N/A	ENSP00000339529.3	Q99575
	POP1	ENST00000916453.1		c.142+296_142+297insA		intron	N/A	ENSP00000586512.1

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

African (AFR) AF: 0.289 AC: 9611 AN: 33250

American (AMR) AF: 0.258 AC: 3102 AN: 12006

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 429 AN: 2890

East Asian (EAS) AF: 0.149 AC: 619 AN: 4152

South Asian (SAS) AF: 0.267 AC: 1054 AN: 3944

European-Finnish (FIN) AF: 0.328 AC: 2231 AN: 6800

Middle Eastern (MID) AF: 0.0872 AC: 19 AN: 218

European-Non Finnish (NFE) AF: 0.273 AC: 15817 AN: 57856

Other (OTH) AF: 0.233 AC: 389 AN: 1670

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
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: rs1274675081; hg19: chr8-99136003;