chr19-2253591-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144616.4(JSRP1):​c.436+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,418,986 control chromosomes in the GnomAD database, including 306,781 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 0.59 ( 27063 hom., cov: 35)
Exomes 𝑓: 0.66 ( 279718 hom. )

Consequence

JSRP1
NM_144616.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.722

Publications

13 publications found
Variant links:
Genes affected
JSRP1 (HGNC:24963): (junctional sarcoplasmic reticulum protein 1) The protein encoded by this gene is involved in excitation-contraction coupling at the sarcoplasmic reticulum. The encoded protein can interact with CACNA1S, CACNB1, and calsequestrin to help regulate calcium influx and efflux in skeletal muscle. [provided by RefSeq, Jul 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JSRP1NM_144616.4 linkc.436+29G>A intron_variant Intron 5 of 6 ENST00000300961.10 NP_653217.1 Q96MG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JSRP1ENST00000300961.10 linkc.436+29G>A intron_variant Intron 5 of 6 2 NM_144616.4 ENSP00000300961.4 Q96MG2
JSRP1ENST00000593238.2 linkn.*78G>A downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.587
AC:
89224
AN:
152078
Hom.:
27075
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.414
Gnomad AMI
AF:
0.521
Gnomad AMR
AF:
0.636
Gnomad ASJ
AF:
0.715
Gnomad EAS
AF:
0.558
Gnomad SAS
AF:
0.600
Gnomad FIN
AF:
0.614
Gnomad MID
AF:
0.763
Gnomad NFE
AF:
0.670
Gnomad OTH
AF:
0.641
GnomAD2 exomes
AF:
0.641
AC:
24471
AN:
38192
AF XY:
0.642
show subpopulations
Gnomad AFR exome
AF:
0.451
Gnomad AMR exome
AF:
0.605
Gnomad ASJ exome
AF:
0.722
Gnomad EAS exome
AF:
0.560
Gnomad FIN exome
AF:
0.626
Gnomad NFE exome
AF:
0.686
Gnomad OTH exome
AF:
0.700
GnomAD4 exome
AF:
0.662
AC:
838431
AN:
1266790
Hom.:
279718
Cov.:
34
AF XY:
0.661
AC XY:
408155
AN XY:
617592
show subpopulations
African (AFR)
AF:
0.410
AC:
10249
AN:
24980
American (AMR)
AF:
0.613
AC:
11228
AN:
18308
Ashkenazi Jewish (ASJ)
AF:
0.709
AC:
13667
AN:
19266
East Asian (EAS)
AF:
0.531
AC:
15322
AN:
28866
South Asian (SAS)
AF:
0.600
AC:
38093
AN:
63476
European-Finnish (FIN)
AF:
0.623
AC:
19370
AN:
31116
Middle Eastern (MID)
AF:
0.749
AC:
3591
AN:
4794
European-Non Finnish (NFE)
AF:
0.676
AC:
691986
AN:
1023498
Other (OTH)
AF:
0.665
AC:
34925
AN:
52486
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
13921
27841
41762
55682
69603
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
18620
37240
55860
74480
93100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.586
AC:
89231
AN:
152196
Hom.:
27063
Cov.:
35
AF XY:
0.586
AC XY:
43559
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.414
AC:
17202
AN:
41556
American (AMR)
AF:
0.636
AC:
9739
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.715
AC:
2482
AN:
3472
East Asian (EAS)
AF:
0.557
AC:
2875
AN:
5162
South Asian (SAS)
AF:
0.600
AC:
2892
AN:
4824
European-Finnish (FIN)
AF:
0.614
AC:
6511
AN:
10612
Middle Eastern (MID)
AF:
0.762
AC:
224
AN:
294
European-Non Finnish (NFE)
AF:
0.669
AC:
45486
AN:
67946
Other (OTH)
AF:
0.637
AC:
1348
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1890
3779
5669
7558
9448
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
752
1504
2256
3008
3760
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.581
Hom.:
7780
Bravo
AF:
0.582
Asia WGS
AF:
0.523
AC:
1822
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
3.0
DANN
Benign
0.94
PhyloP100
-0.72
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3746158; hg19: chr19-2253590; API