chr8-74282478-T-C

Variant names:

• chr8-74282478-T-C
• rs971462
• NM_020647.4:c.1140-22975A>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.1140-22975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,082 control chromosomes in the GnomAD database, including 10,244 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 0.36 (10244 hom., cov: 33)
• Consequence: JPH1 NM_020647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.475 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.1140-22975A>G		intron	N/A	NP_065698.1	Q9HDC5
	JPH1	NM_001317830.2		c.1140-22975A>G		intron	N/A	NP_001304759.1	Q9HDC5
	JPH1	NM_001363050.1		c.1140-22975A>G		intron	N/A	NP_001349979.1	Q9HDC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH1	ENST00000342232.5	TSL:1 MANE Select	c.1140-22975A>G		intron	N/A	ENSP00000344488.4	Q9HDC5
	JPH1	ENST00000519947.1	TSL:1	n.*535-22975A>G		intron	N/A	ENSP00000429652.1	E5RHU9
	JPH1	ENST00000868437.1		c.1140-22975A>G		intron	N/A	ENSP00000538496.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55143 AN: 151964 Hom.: 10221 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.363 AC: 55218 AN: 152082 Hom.: 10244 Cov.: 33 AF XY: 0.363 AC XY: 26985 AN XY: 74330

African (AFR) AF: 0.313 AC: 12971 AN: 41498

American (AMR) AF: 0.355 AC: 5423 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1164 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1478 AN: 5178

South Asian (SAS) AF: 0.492 AC: 2368 AN: 4814

European-Finnish (FIN) AF: 0.350 AC: 3695 AN: 10552

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26867 AN: 67974

Other (OTH) AF: 0.363 AC: 767 AN: 2114

Alfa AF: 0.360 Hom.: 1616

Bravo AF: 0.355

Asia WGS AF: 0.388 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.73
PhyloP100		-0.30
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: rs971462; hg19: chr8-75194713;