dbSNP rs7250822: JSRP1:p.Met1? (chr19-2255312-C-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_SupportingBA1

The NM_144616.4(JSRP1):c.3G>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,605,768 control chromosomes in the GnomAD database, including 9,892 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 0.16 ( 4189 hom., cov: 32)

Exomes 𝑓: 0.047 ( 5703 hom. )

Consequence

JSRP1
NM_144616.4 start_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00100

Publications

10 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 -7 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 3 codons. Genomic position: 2255308. Lost 0.007 part of the original CDS.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JSRP1	NM_144616.4 link	c.3G>C	p.Met1?	start_lost	Exon 2 of 7	ENST00000300961.10	NP_653217.1	Q96MG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000300961.10 link	c.3G>C	p.Met1?	start_lost	Exon 2 of 7	2	NM_144616.4	ENSP00000300961.4		Q96MG2
JSRP1	ENST00000593238.2 link	n.459G>C		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23626

AN:

152060

Hom.:

4183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.0883

AC:

21554

AN:

244088

AF XY:

0.0805

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.00607

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0596

GnomAD4 exome

AF:

0.0466

AC:

67725

AN:

1453590

Hom.:

5703

Cov.:

AF XY:

0.0468

AC XY:

33839

AN XY:

723100

show subpopulations

African (AFR)

AF:

0.431

AC:

14284

AN:

33114

American (AMR)

AF:

0.119

AC:

5276

AN:

44164

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

905

AN:

25956

East Asian (EAS)

AF:

0.220

AC:

8658

AN:

39378

South Asian (SAS)

AF:

0.110

AC:

9420

AN:

85652

European-Finnish (FIN)

AF:

0.00675

AC:

352

AN:

52142

Middle Eastern (MID)

AF:

0.0590

AC:

317

AN:

5370

European-Non Finnish (NFE)

AF:

0.0219

AC:

24242

AN:

1107830

Other (OTH)

AF:

0.0712

AC:

4271

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2395

4789

7184

9578

11973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

23674

AN:

152178

Hom.:

4189

Cov.:

AF XY:

0.155

AC XY:

11561

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.420

AC:

17436

AN:

41490

American (AMR)

AF:

0.155

AC:

2368

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3466

East Asian (EAS)

AF:

0.238

AC:

1229

AN:

5160

South Asian (SAS)

AF:

0.120

AC:

581

AN:

4828

European-Finnish (FIN)

AF:

0.00773

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0227

AC:

1546

AN:

68014

Other (OTH)

AF:

0.131

AC:

277

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

798

1596

2394

3192

3990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0562

Hom.:

345

Bravo

AF:

0.176

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.413

AC:

1817

ESP6500EA

AF:

0.0243

AC:

209

ExAC

AF:

0.0909

AC:

10997

Asia WGS

AF:

0.227

AC:

787

AN:

3478

EpiCase

AF:

0.0260

EpiControl

AF:

0.0243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.54

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.025

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0017

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0010

MetaSVM

Benign

-0.92

PhyloP100

0.0010

PROVEAN

Benign

-0.060

REVEL

Benign

0.091

Sift

Benign

1.0

Sift4G

Benign

0.86

Polyphen

0.0

Vest4

0.019

MutPred

0.49

Loss of disorder (P = 0.0385);

ClinPred

0.0016

GERP RS

1.7

Varity_R

0.063

gMVP

0.062

Mutation Taster

=197/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs7250822

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