Genetic Variant JSRP1:c.436+29G>A (chr19-2253591-C-T) – ACMG Classification: Benign (-12 pts)

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

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]

JSRP1 links:

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
JSRP1	NM_144616.4 link	c.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
JSRP1	ENST00000300961.10 link	c.436+29G>A		intron_variant	Intron 5 of 6	2	NM_144616.4	ENSP00000300961.4		Q96MG2
JSRP1	ENST00000593238.2 link	n.*78G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89224

AN:

152078

Hom.:

27075

Cov.:

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.:

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

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

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.:

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

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

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

(source)

DANN

Benign

0.94

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over