19-2260362-C-T

Position:

• chr19-2260362-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593238.2(JSRP1):​n.427-5018G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,970 control chromosomes in the GnomAD database, including 2,572 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 0.13 (2572 hom., cov: 31)
• Consequence: JSRP1 ENST00000593238.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000593238.2	n.427-5018G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20068 AN: 151852 Hom.: 2559 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.132 AC: 20132 AN: 151970 Hom.: 2572 Cov.: 31 AF XY: 0.133 AC XY: 9917 AN XY: 74294

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0320

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0471 Hom.: 584

Bravo AF: 0.147

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4806834; hg19: chr19-2260361;