rs3115883

Variant names:

• chr15-42409490-T-A
• rs3115883
• NM_000070.3:c.1992+110T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-42409490-T-A
• chr15-42409490-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000070.3(CAPN3):​c.1992+110T>A 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAPN3 NM_000070.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 7 publications found

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]

CAPN3 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• muscular dystrophy, limb-girdle, autosomal dominant 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000258461 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN3	NM_000070.3	c.1992+110T>A		intron_variant	Intron 17 of 23	ENST00000397163.8	NP_000061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN3	ENST00000397163.8	c.1992+110T>A		intron_variant	Intron 17 of 23	1	NM_000070.3	ENSP00000380349.3
CAPN3	ENST00000673886.1	c.-4+110T>A		intron_variant	Intron 4 of 10			ENSP00000501155.1
CAPN3	ENST00000673928.1	c.-4+110T>A		intron_variant	Intron 4 of 10			ENSP00000501099.1
CAPN3	ENST00000674146.1	c.-4+110T>A		intron_variant	Intron 5 of 11			ENSP00000501175.1
CAPN3	ENST00000674149.1	c.-4+110T>A		intron_variant	Intron 4 of 10			ENSP00000501112.1
CAPN3	ENST00000673743.1	c.-101+110T>A		intron_variant	Intron 4 of 10			ENSP00000500989.1
ENSG00000258461	ENST00000495723.1	n.*2428+110T>A		intron_variant	Intron 19 of 25	2		ENSP00000492063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 958876 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 492272

African (AFR) AF: 0.00 AC: 0 AN: 23530

American (AMR) AF: 0.00 AC: 0 AN: 36090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22486

East Asian (EAS) AF: 0.00 AC: 0 AN: 35032

South Asian (SAS) AF: 0.00 AC: 0 AN: 71378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 671782

Other (OTH) AF: 0.00 AC: 0 AN: 43650

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.046
DANN	Benign	0.64
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs3115883; hg19: chr15-42701688;