rs2412710

chr15-42391589-G-A

Variant summary

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

The NM_000070.3(CAPN3):c.946-1050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 152,218 control chromosomes in the GnomAD database, including 167 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 0.035 (167 hom., cov: 31)
• Consequence: CAPN3 NM_000070.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

Genes affected

CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]

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 = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN3	NM_000070.3	c.946-1050G>A		intron_variant		ENST00000397163.8
CAPN3	NM_024344.2	c.946-1050G>A		intron_variant
CAPN3	NM_173087.2	c.802-1050G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN3	ENST00000397163.8	c.946-1050G>A		intron_variant		1	NM_000070.3	P2

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5361 AN: 152100 Hom.: 164 Cov.: 31

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0353 AC: 5375 AN: 152218 Hom.: 167 Cov.: 31 AF XY: 0.0346 AC XY: 2575 AN XY: 74422

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0220 Hom.: 65

Bravo AF: 0.0396

Asia WGS AF: 0.00953 AC: 33 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	0.016
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2412710; hg19: chr15-42683787;