rs6073330

chr20-44108854-C-A

Variant summary

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

The NM_020433.5(JPH2):c.*4664G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,868 control chromosomes in the GnomAD database, including 6,849 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 0.29 (6849 hom., cov: 31)
• Consequence: JPH2 NM_020433.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

Genes affected

JPH2 (HGNC:14202): (junctophilin 2) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH2	NM_020433.5	c.*4664G>T		3_prime_UTR_variant	6/6	ENST00000372980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.*4664G>T		3_prime_UTR_variant	6/6	5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44550 AN: 151750 Hom.: 6840 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.294 AC: 44591 AN: 151868 Hom.: 6849 Cov.: 31 AF XY: 0.295 AC XY: 21900 AN XY: 74244

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.291

Alfa AF: 0.273 Hom.: 11786

Bravo AF: 0.302

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.4
Dann	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6073330; hg19: chr20-42737494;