rs11844366

Variant names:

• chr14-23572415-T-C
• rs11844366
• NM_001146028.2:c.1152-495A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146028.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH4	NM_001146028.2	MANE Select	c.1152-495A>G		intron	N/A	NP_001139500.1
	JPH4	NM_032452.3		c.1152-495A>G		intron	N/A	NP_115828.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH4	ENST00000356300.9	TSL:1 MANE Select	c.1152-495A>G		intron	N/A	ENSP00000348648.4
	JPH4	ENST00000397118.7	TSL:1	c.1152-495A>G		intron	N/A	ENSP00000380307.3
	JPH4	ENST00000544177.1	TSL:2	c.146+418A>G		intron	N/A	ENSP00000439562.1

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

African (AFR) AF: 0.582 AC: 23956 AN: 41156

American (AMR) AF: 0.149 AC: 2282 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 308 AN: 3464

East Asian (EAS) AF: 0.196 AC: 1009 AN: 5140

South Asian (SAS) AF: 0.203 AC: 977 AN: 4804

European-Finnish (FIN) AF: 0.240 AC: 2527 AN: 10534

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10400 AN: 67874

Other (OTH) AF: 0.220 AC: 465 AN: 2112

Alfa AF: 0.199 Hom.: 9295

Bravo AF: 0.286

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		-0.38
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: rs11844366; hg19: chr14-24041624;