rs4738442

Variant names:

• chr8-74295218-T-C
• rs4738442
• NM_020647.4:c.1139+19643A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-74295218-T-C
• chr8-74295218-T-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.1139+19643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,286 control chromosomes in the GnomAD database, including 348 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 0.046 (348 hom., cov: 32)
• Consequence: JPH1 NM_020647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH1	NM_020647.4	MANE Select	c.1139+19643A>G		intron	N/A	NP_065698.1
	JPH1	NM_001317830.2		c.1139+19643A>G		intron	N/A	NP_001304759.1
	JPH1	NM_001363050.1		c.1139+19643A>G		intron	N/A	NP_001349979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH1	ENST00000342232.5	TSL:1 MANE Select	c.1139+19643A>G		intron	N/A	ENSP00000344488.4
	JPH1	ENST00000519947.1	TSL:1	n.*534+19643A>G		intron	N/A	ENSP00000429652.1
	JPH1	ENST00000868437.1		c.1139+19643A>G		intron	N/A	ENSP00000538496.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7059 AN: 152168 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0464 AC: 7067 AN: 152286 Hom.: 348 Cov.: 32 AF XY: 0.0479 AC XY: 3570 AN XY: 74464

African (AFR) AF: 0.0113 AC: 470 AN: 41568

American (AMR) AF: 0.108 AC: 1648 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1252 AN: 5176

South Asian (SAS) AF: 0.0345 AC: 166 AN: 4816

European-Finnish (FIN) AF: 0.0285 AC: 303 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2906 AN: 68026

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0481 Hom.: 626

Bravo AF: 0.0543

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.80
PhyloP100		-0.044
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: rs4738442; hg19: chr8-75207453;