rs875142

Positions:

• chr6-52363427-A-G

Variant summary

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

The ENST00000442253.3(PAQR8):​c.-53+1178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,024 control chromosomes in the GnomAD database, including 8,284 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 0.32 (8284 hom., cov: 32)
• Consequence: PAQR8 ENST00000442253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

Genes affected

PAQR8 (HGNC:15708): (progestin and adipoQ receptor family member 8) Predicted to enable steroid binding activity and steroid hormone receptor activity. Predicted to be involved in response to steroid hormone. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAQR8	NM_133367.5	c.-53+1178A>G		intron_variant		ENST00000442253.3	NP_588608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAQR8	ENST00000442253.3	c.-53+1178A>G		intron_variant		1	NM_133367.5	ENSP00000406197	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47983 AN: 151906 Hom.: 8276 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.316 AC: 48023 AN: 152024 Hom.: 8284 Cov.: 32 AF XY: 0.319 AC XY: 23733 AN XY: 74294

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.352

Alfa AF: 0.276 Hom.: 7031

Bravo AF: 0.343

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.66

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: rs875142; hg19: chr6-52228225;