rs875142

Variant names:

• chr6-52363427-A-G
• rs875142
• NM_133367.5:c.-53+1178A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133367.5(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 NM_133367.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 9 publications found

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]

EFHC1 Gene-Disease associations (from GenCC):

• juvenile myoclonic epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000295329 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133367.5. 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
	PAQR8	NM_133367.5	MANE Select	c.-53+1178A>G		intron	N/A	NP_588608.1	Q8TEZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAQR8	ENST00000442253.3	TSL:1 MANE Select	c.-53+1178A>G		intron	N/A	ENSP00000406197.2	Q8TEZ7
	PAQR8	ENST00000360726.3	TSL:1	c.-132+936A>G		intron	N/A	ENSP00000353953.3	Q8TEZ7
	EFHC1	ENST00000635760.1	TSL:5	c.-262+1178A>G		intron	N/A	ENSP00000489765.1	A0A1B0GTM7

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

African (AFR) AF: 0.423 AC: 17518 AN: 41422

American (AMR) AF: 0.434 AC: 6640 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3460

East Asian (EAS) AF: 0.358 AC: 1849 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1613 AN: 4824

European-Finnish (FIN) AF: 0.191 AC: 2015 AN: 10568

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16042 AN: 67990

Other (OTH) AF: 0.352 AC: 740 AN: 2102

Alfa AF: 0.280 Hom.: 10063

Bravo AF: 0.343

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.47
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: rs875142; hg19: chr6-52228225;