19-2260362-C-T

Variant names:

• chr19-2260362-C-T
• rs4806834
• ENST00000593238.2:n.427-5018G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000593238.2(JSRP1):​n.427-5018G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000593238.2	n.427-5018G>A		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.321 AC: 13259 AN: 41360

American (AMR) AF: 0.149 AC: 2277 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1162 AN: 5176

South Asian (SAS) AF: 0.118 AC: 569 AN: 4816

European-Finnish (FIN) AF: 0.0327 AC: 346 AN: 10596

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0320 AC: 2172 AN: 67980

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.0568 Hom.: 1900

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
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs4806834; hg19: chr19-2260361;