rs6073358

chr20-44174096-C-T

Variant summary

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

The NM_020433.5(JPH2):c.379+12231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,254 control chromosomes in the GnomAD database, including 548 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 0.077 (548 hom., cov: 32)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH2	NM_020433.5	c.379+12231G>A		intron_variant		ENST00000372980.4
JPH2	XM_006723833.5	c.*7410G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.379+12231G>A		intron_variant		5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11731 AN: 152134 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0887

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

GnomAD4 genome AF: 0.0771 AC: 11737 AN: 152254 Hom.: 548 Cov.: 32 AF XY: 0.0807 AC XY: 6003 AN XY: 74432

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0179

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.0877

Alfa AF: 0.0912 Hom.: 889

Bravo AF: 0.0691

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.2
Dann	Benign	0.54

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: rs6073358; hg19: chr20-42802736;