rs10504566

chr8-74263871-A-Gchr8-74263871-A-T

Variant summary

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

The NM_020647.4(JPH1):c.1140-4368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,198 control chromosomes in the GnomAD database, including 957 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 0.070 (957 hom., cov: 32)
• Consequence: JPH1 NM_020647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

JPH1 (HGNC:14201): (junctophilin 1) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH1	NM_020647.4	c.1140-4368T>C		intron_variant		ENST00000342232.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH1	ENST00000342232.5	c.1140-4368T>C		intron_variant		1	NM_020647.4	P1
JPH1	ENST00000519947.1	c.*535-4368T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10645 AN: 152080 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0702 AC: 10690 AN: 152198 Hom.: 957 Cov.: 32 AF XY: 0.0689 AC XY: 5125 AN XY: 74422

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.00989

Gnomad4 NFE AF: 0.00800

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0117 Hom.: 14

Bravo AF: 0.0783

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	13
Dann	Benign	0.70

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: rs10504566; hg19: chr8-75176106;