NM_020647.4:c.1140-5350C>G

Variant names:

• chr8-74264853-G-C
• rs10504567
• NM_020647.4:c.1140-5350C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020647.4(JPH1):​c.1140-5350C>G 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 152,166 control chromosomes in the GnomAD database, including 956 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 (956 hom., cov: 32)
• Consequence: JPH1 NM_020647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 0 publications found

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]

JPH1 Gene-Disease associations (from GenCC):

• congenital myopathy 25

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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 rank	MANE	Protein	UniProt
JPH1	NM_020647.4	c.1140-5350C>G		intron_variant	Intron 2 of 5	ENST00000342232.5	NP_065698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH1	ENST00000342232.5	c.1140-5350C>G		intron_variant	Intron 2 of 5	1	NM_020647.4	ENSP00000344488.4
JPH1	ENST00000519947.1	n.*535-5350C>G		intron_variant	Intron 2 of 4	1		ENSP00000429652.1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10637 AN: 152048 Hom.: 949 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: 0.0843

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0100

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00798

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: 10682 AN: 152166 Hom.: 956 Cov.: 32 AF XY: 0.0688 AC XY: 5116 AN XY: 74404

African (AFR) AF: 0.203 AC: 8433 AN: 41466

American (AMR) AF: 0.0354 AC: 542 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 210 AN: 3468

East Asian (EAS) AF: 0.0845 AC: 438 AN: 5182

South Asian (SAS) AF: 0.0531 AC: 256 AN: 4818

European-Finnish (FIN) AF: 0.0100 AC: 106 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00798 AC: 543 AN: 68012

Other (OTH) AF: 0.0629 AC: 133 AN: 2114

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	-0.84
CADD	Benign	7.8
DANN	Benign	0.54
PhyloP100		0.27
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: rs10504567; hg19: chr8-75177088;