19-2253591-C-T

Position:

• chr19-2253591-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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=-0.72).
• 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/exons	MANE	Protein	UniProt
JSRP1	NM_144616.4	c.436+29G>A		intron_variant		ENST00000300961.10	NP_653217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000300961.10	c.436+29G>A		intron_variant		2	NM_144616.4	ENSP00000300961.4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89224 AN: 152078 Hom.: 27075 Cov.: 35

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

GnomAD3 exomes AF: 0.641 AC: 24471 AN: 38192 Hom.: 8004 AF XY: 0.642 AC XY: 14248 AN XY: 22180

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 SAS exome AF: 0.618

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.: 34 AF XY: 0.661 AC XY: 408155 AN XY: 617592

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.531

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.586 AC: 89231 AN: 152196 Hom.: 27063 Cov.: 35 AF XY: 0.586 AC XY: 43559 AN XY: 74394

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.637

Alfa AF: 0.587 Hom.: 6975

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
DANN	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs3746158; hg19: chr19-2253590;