20-44114607-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020433.5(JPH2):​c.*14+175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 122,012 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 4 hom., cov: 28)

Consequence

JPH2
NM_020433.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.596
Variant links:
Genes affected
JPH2 (HGNC:14202): (junctophilin 2) 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. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 20-44114607-T-C is Benign according to our data. Variant chr20-44114607-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1211441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00715 (872/122012) while in subpopulation SAS AF= 0.0105 (40/3800). AF 95% confidence interval is 0.00795. There are 4 homozygotes in gnomad4. There are 452 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JPH2NM_020433.5 linkuse as main transcriptc.*14+175A>G intron_variant ENST00000372980.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JPH2ENST00000372980.4 linkuse as main transcriptc.*14+175A>G intron_variant 5 NM_020433.5 P1Q9BR39-1

Frequencies

GnomAD3 genomes
AF:
0.00713
AC:
870
AN:
121936
Hom.:
4
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.00851
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00406
Gnomad ASJ
AF:
0.0168
Gnomad EAS
AF:
0.00374
Gnomad SAS
AF:
0.0111
Gnomad FIN
AF:
0.0166
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00544
Gnomad OTH
AF:
0.00423
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00715
AC:
872
AN:
122012
Hom.:
4
Cov.:
28
AF XY:
0.00764
AC XY:
452
AN XY:
59166
show subpopulations
Gnomad4 AFR
AF:
0.00862
Gnomad4 AMR
AF:
0.00406
Gnomad4 ASJ
AF:
0.0168
Gnomad4 EAS
AF:
0.00375
Gnomad4 SAS
AF:
0.0105
Gnomad4 FIN
AF:
0.0166
Gnomad4 NFE
AF:
0.00544
Gnomad4 OTH
AF:
0.00419
Alfa
AF:
0.00923
Hom.:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 13, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.1
DANN
Benign
0.78

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs398040671; hg19: chr20-42743247; API