rs11844366

chr14-23572415-T-C

Variant summary

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

The NM_001146028.2(JPH4):c.1152-495A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,558 control chromosomes in the GnomAD database, including 8,646 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 0.28 (8646 hom., cov: 30)
• Consequence: JPH4 NM_001146028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

Genes affected

JPH4 (HGNC:20156): (junctophilin 4) This gene encodes a member of the junctophilin family of transmembrane proteins that are involved in the formation of the junctional membrane complexes between the plasma membrane and the endoplasmic/sarcoplasmic reticulum in excitable cells. The encoded protein contains a conserved N-terminal repeat region called the membrane occupation and recognition nexus sequence that is found in other members of the junctophilin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

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 (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH4	NM_001146028.2	c.1152-495A>G		intron_variant		ENST00000356300.9
JPH4	NM_032452.3	c.1152-495A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH4	ENST00000356300.9	c.1152-495A>G		intron_variant		1	NM_001146028.2	P1
JPH4	ENST00000397118.7	c.1152-495A>G		intron_variant		1		P1
JPH4	ENST00000544177.1	c.146+418A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42093 AN: 151440 Hom.: 8615 Cov.: 30

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0889

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.278 AC: 42172 AN: 151558 Hom.: 8646 Cov.: 30 AF XY: 0.277 AC XY: 20528 AN XY: 74038

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0889

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.220

Alfa AF: 0.181 Hom.: 1978

Bravo AF: 0.286

Asia WGS AF: 0.203 AC: 705 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	4.5
Dann	Benign	0.62

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: rs11844366; hg19: chr14-24041624;