rs10504568

chr8-74264895-T-G

Variant summary

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

The NM_020647.4(JPH1):c.1140-5392A>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 152,216 control chromosomes in the GnomAD database, including 955 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 (955 hom., cov: 32)
• Consequence: JPH1 NM_020647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.91).
• 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.1140-5392A>C		intron_variant		ENST00000342232.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH1	ENST00000342232.5	c.1140-5392A>C		intron_variant		1	NM_020647.4	P1
JPH1	ENST00000519947.1	c.*535-5392A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10643 AN: 152098 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.00988

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00798

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0702 AC: 10688 AN: 152216 Hom.: 955 Cov.: 32 AF XY: 0.0688 AC XY: 5118 AN XY: 74440

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0606

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.00988

Gnomad4 NFE AF: 0.00799

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0427 Hom.: 66

Bravo AF: 0.0784

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	-0.91
Cadd	Benign	9.9
Dann	Benign	0.28

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: rs10504568; hg19: chr8-75177130;