rs8034725

Positions:

• chr15-69314389-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017705.4(PAQR5):​c.-277+15333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 152,172 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (374 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: PAQR5 NM_017705.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

Genes affected

PAQR5 (HGNC:29645): (progestin and adipoQ receptor family member 5) Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAQR5	NM_017705.4	c.-277+15333T>C		intron_variant		ENST00000395407.7	NP_060175.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAQR5	ENST00000395407.7	c.-277+15333T>C		intron_variant		1	NM_017705.4	ENSP00000378803	P1
PAQR5	ENST00000558684.5	c.-243+15333T>C		intron_variant		5		ENSP00000453009
PAQR5	ENST00000561153.5			upstream_gene_variant		5		ENSP00000453526	P1

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7406 AN: 152032 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0488 AC: 7430 AN: 152150 Hom.: 374 Cov.: 32 AF XY: 0.0508 AC XY: 3779 AN XY: 74390

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.00760

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0302 Hom.: 20

Bravo AF: 0.0544

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8034725; hg19: chr15-69606728;