chr19-2255337-A-G

Variant names:

• chr19-2255337-A-G
• rs886363
• NM_144616.4:c.-23T>C

Variant summary

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

The NM_144616.4(JSRP1):​c.-23T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 1,547,316 control chromosomes in the GnomAD database, including 524,754 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 0.86 (56837 hom., cov: 33)
  • Exomes 𝑓: 0.82 (467917 hom.)
• Consequence: JSRP1 NM_144616.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JSRP1	NM_144616.4	c.-23T>C		5_prime_UTR_variant	Exon 2 of 7	ENST00000300961.10	NP_653217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000300961.10	c.-23T>C		5_prime_UTR_variant	Exon 2 of 7	2	NM_144616.4	ENSP00000300961.4
JSRP1	ENST00000593238.2	n.434T>C		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130779 AN: 152056 Hom.: 56782 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.880

GnomAD3 exomes AF: 0.828 AC: 189429 AN: 228902 Hom.: 78800 AF XY: 0.828 AC XY: 103966 AN XY: 125626

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.903

Gnomad EAS exome AF: 0.916

Gnomad SAS exome AF: 0.859

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.845

GnomAD4 exome AF: 0.818 AC: 1140832 AN: 1395142 Hom.: 467917 Cov.: 20 AF XY: 0.818 AC XY: 568635 AN XY: 694794

Gnomad4 AFR exome AF: 0.974

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.903

Gnomad4 EAS exome AF: 0.916

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.806

Gnomad4 OTH exome AF: 0.849

GnomAD4 genome AF: 0.860 AC: 130894 AN: 152174 Hom.: 56837 Cov.: 33 AF XY: 0.859 AC XY: 63895 AN XY: 74398

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.883

Alfa AF: 0.816 Hom.: 13304

Bravo AF: 0.874

Asia WGS AF: 0.901 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs886363; hg19: chr19-2255336; COSMIC: COSV55560564; COSMIC: COSV55560564;