rs8034725

Variant names:

• chr15-69314389-T-C
• rs8034725
• NM_017705.4:c.-277+15333T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAQR5	NM_017705.4	c.-277+15333T>C		intron_variant	Intron 1 of 8	ENST00000395407.7	NP_060175.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAQR5	ENST00000395407.7	c.-277+15333T>C		intron_variant	Intron 1 of 8	1	NM_017705.4	ENSP00000378803.2
PAQR5	ENST00000558684.5	c.-243+15333T>C		intron_variant	Intron 1 of 4	5		ENSP00000453009.1
PAQR5	ENST00000561153.5	c.-686T>C		upstream_gene_variant		5		ENSP00000453526.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0625 AC: 1 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.107 AC: 4446 AN: 41480

American (AMR) AF: 0.0565 AC: 863 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3466

East Asian (EAS) AF: 0.150 AC: 771 AN: 5156

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4826

European-Finnish (FIN) AF: 0.0478 AC: 507 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00760 AC: 517 AN: 68014

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0327 Hom.: 23

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
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8034725; hg19: chr15-69606728;