ENST00000495723.1:n.*3036C>T

Variant names:

• chr15-42411907-C-T
• rs3098423
• ENST00000495723.1:n.*3036C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000495723.1(ENSG00000258461):​n.*3036C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,569,722 control chromosomes in the GnomAD database, including 740,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72904 hom., cov: 30)
  • Exomes 𝑓: 0.97 (667213 hom.)
• Consequence: ENSG00000258461 ENST00000495723.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.982
• Publications: 14 publications found

Genes affected

ENSG00000258461 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-42411907-C-T is Benign according to our data. Variant chr15-42411907-C-T is described in ClinVar as Benign. ClinVar VariationId is 286594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495723.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN3	NM_000070.3	MANE Select	c.*134C>T		3_prime_UTR	Exon 24 of 24	NP_000061.1
	CAPN3	NM_024344.2		c.*134C>T		3_prime_UTR	Exon 23 of 23	NP_077320.1
	CAPN3	NM_173087.2		c.*134C>T		3_prime_UTR	Exon 21 of 21	NP_775110.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258461	ENST00000495723.1	TSL:2	n.*3036C>T		non_coding_transcript_exon	Exon 26 of 26	ENSP00000492063.1
	CAPN3	ENST00000397163.8	TSL:1 MANE Select	c.*134C>T		3_prime_UTR	Exon 24 of 24	ENSP00000380349.3
	CAPN3	ENST00000357568.8	TSL:1	c.*134C>T		3_prime_UTR	Exon 23 of 23	ENSP00000350181.3

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148836 AN: 152100 Hom.: 72844 Cov.: 30

Gnomad AFR AF: 0.995

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.942

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.981

GnomAD4 exome AF: 0.970 AC: 1375192 AN: 1417504 Hom.: 667213 Cov.: 49 AF XY: 0.971 AC XY: 680719 AN XY: 701174

African (AFR) AF: 0.996 AC: 32330 AN: 32472

American (AMR) AF: 0.994 AC: 36878 AN: 37118

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 25033 AN: 25144

East Asian (EAS) AF: 1.00 AC: 37523 AN: 37526

South Asian (SAS) AF: 0.997 AC: 80825 AN: 81074

European-Finnish (FIN) AF: 0.940 AC: 47733 AN: 50756

Middle Eastern (MID) AF: 0.998 AC: 5694 AN: 5704

European-Non Finnish (NFE) AF: 0.966 AC: 1051841 AN: 1088854

Other (OTH) AF: 0.974 AC: 57335 AN: 58856

GnomAD4 genome AF: 0.979 AC: 148955 AN: 152218 Hom.: 72904 Cov.: 30 AF XY: 0.978 AC XY: 72782 AN XY: 74416

African (AFR) AF: 0.995 AC: 41313 AN: 41534

American (AMR) AF: 0.991 AC: 15154 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3460 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 0.997 AC: 4809 AN: 4822

European-Finnish (FIN) AF: 0.942 AC: 9984 AN: 10604

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65780 AN: 68000

Other (OTH) AF: 0.982 AC: 2075 AN: 2114

Alfa AF: 0.976 Hom.: 108474

Bravo AF: 0.983

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2A (2)
-	-	2	not provided (2)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Muscular dystrophy, limb-girdle, autosomal dominant 4 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs3098423; hg19: chr15-42704105;