rs11604536

Variant names:

• chr11-77116314-A-G
• rs11604536
• NM_004055.5:c.971+11A>G

Variant summary

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

The NM_004055.5(CAPN5):​c.971+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,607,764 control chromosomes in the GnomAD database, including 60,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7982 hom., cov: 33)
  • Exomes 𝑓: 0.26 (52578 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.80
• Publications: 9 publications found

Genes affected

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 Gene-Disease associations (from GenCC):

• CAPN5-related vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant neovascular inflammatory vitreoretinopathy

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-77116314-A-G is Benign according to our data. Variant chr11-77116314-A-G is described in ClinVar as Benign. ClinVar VariationId is 259225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.971+11A>G		intron_variant	Intron 7 of 12	ENST00000648180.1	NP_004046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.971+11A>G		intron_variant	Intron 7 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47001 AN: 151810 Hom.: 7958 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.284 AC: 69156 AN: 243598 AF XY: 0.281

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.417

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.264 AC: 384135 AN: 1455834 Hom.: 52578 Cov.: 31 AF XY: 0.265 AC XY: 191904 AN XY: 723956

African (AFR) AF: 0.459 AC: 15306 AN: 33370

American (AMR) AF: 0.279 AC: 12354 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4312 AN: 26082

East Asian (EAS) AF: 0.426 AC: 16871 AN: 39558

South Asian (SAS) AF: 0.322 AC: 27477 AN: 85422

European-Finnish (FIN) AF: 0.223 AC: 11873 AN: 53186

Middle Eastern (MID) AF: 0.271 AC: 1560 AN: 5746

European-Non Finnish (NFE) AF: 0.251 AC: 278250 AN: 1108044

Other (OTH) AF: 0.268 AC: 16132 AN: 60166

GnomAD4 genome AF: 0.310 AC: 47084 AN: 151930 Hom.: 7982 Cov.: 33 AF XY: 0.308 AC XY: 22875 AN XY: 74248

African (AFR) AF: 0.448 AC: 18525 AN: 41394

American (AMR) AF: 0.250 AC: 3820 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3466

East Asian (EAS) AF: 0.432 AC: 2217 AN: 5136

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2383 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17218 AN: 67920

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.287 Hom.: 2651

Bravo AF: 0.318

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		-1.8
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: rs11604536; hg19: chr11-76827360; COSMIC: COSV53686697; COSMIC: COSV53686697;