NM_144616.4:c.436+29G>A

Variant names:

• chr19-2253591-C-T
• rs3746158
• NM_144616.4:c.436+29G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144616.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JSRP1	NM_144616.4	MANE Select	c.436+29G>A		intron	N/A	NP_653217.1	Q96MG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JSRP1	ENST00000300961.10	TSL:2 MANE Select	c.436+29G>A		intron	N/A	ENSP00000300961.4	Q96MG2
	JSRP1	ENST00000862809.1		c.457+8G>A		splice_region intron	N/A	ENSP00000532868.1
	JSRP1	ENST00000967628.1		c.457+29G>A		intron	N/A	ENSP00000637687.1

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

GnomAD2 exomes AF: 0.641 AC: 24471 AN: 38192 AF XY: 0.642

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 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

African (AFR) AF: 0.410 AC: 10249 AN: 24980

American (AMR) AF: 0.613 AC: 11228 AN: 18308

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 13667 AN: 19266

East Asian (EAS) AF: 0.531 AC: 15322 AN: 28866

South Asian (SAS) AF: 0.600 AC: 38093 AN: 63476

European-Finnish (FIN) AF: 0.623 AC: 19370 AN: 31116

Middle Eastern (MID) AF: 0.749 AC: 3591 AN: 4794

European-Non Finnish (NFE) AF: 0.676 AC: 691986 AN: 1023498

Other (OTH) AF: 0.665 AC: 34925 AN: 52486

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

African (AFR) AF: 0.414 AC: 17202 AN: 41556

American (AMR) AF: 0.636 AC: 9739 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2875 AN: 5162

South Asian (SAS) AF: 0.600 AC: 2892 AN: 4824

European-Finnish (FIN) AF: 0.614 AC: 6511 AN: 10612

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45486 AN: 67946

Other (OTH) AF: 0.637 AC: 1348 AN: 2116

Alfa AF: 0.581 Hom.: 7780

Bravo AF: 0.582

Asia WGS AF: 0.523 AC: 1822 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.94
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746158; hg19: chr19-2253590;