chr15-42409920-C-G

Variant names:

• chr15-42409920-C-G
• NM_000070.3:c.2051-11C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000070.3(CAPN3):​c.2051-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CAPN3 NM_000070.3 intron
• Scores: Splicing: ADA: 0.009830
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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]

ENSG00000258461 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN3	NM_000070.3	c.2051-11C>G		intron_variant	Intron 18 of 23	ENST00000397163.8	NP_000061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN3	ENST00000397163.8	c.2051-11C>G		intron_variant	Intron 18 of 23	1	NM_000070.3	ENSP00000380349.3
CAPN3	ENST00000673886.1	c.56-11C>G		intron_variant	Intron 5 of 10			ENSP00000501155.1
CAPN3	ENST00000673928.1	c.56-11C>G		intron_variant	Intron 5 of 10			ENSP00000501099.1
CAPN3	ENST00000674146.1	c.56-11C>G		intron_variant	Intron 6 of 11			ENSP00000501175.1
CAPN3	ENST00000674149.1	c.56-11C>G		intron_variant	Intron 5 of 10			ENSP00000501112.1
CAPN3	ENST00000673743.1	c.-42-16C>G		intron_variant	Intron 5 of 10			ENSP00000500989.1
ENSG00000258461	ENST00000495723.1	n.*2487-11C>G		intron_variant	Intron 20 of 25	2		ENSP00000492063.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0098
dbscSNV1_RF	Benign	0.27
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42702118;