rs11237081

Variant names:

• chr11-77083706-G-C
• rs11237081
• NM_004055.5:c.-35-1146G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004055.5(CAPN5):​c.-35-1146G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,056 control chromosomes in the GnomAD database, including 11,418 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 0.37 (11418 hom., cov: 32)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.-35-1146G>C		intron_variant	Intron 1 of 12	ENST00000648180.1	NP_004046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.-35-1146G>C		intron_variant	Intron 1 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56079 AN: 151938 Hom.: 11419 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.369 AC: 56084 AN: 152056 Hom.: 11418 Cov.: 32 AF XY: 0.369 AC XY: 27439 AN XY: 74306

African (AFR) AF: 0.204 AC: 8476 AN: 41482

American (AMR) AF: 0.338 AC: 5172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5166

South Asian (SAS) AF: 0.434 AC: 2093 AN: 4824

European-Finnish (FIN) AF: 0.501 AC: 5298 AN: 10578

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30913 AN: 67942

Other (OTH) AF: 0.366 AC: 771 AN: 2106

Alfa AF: 0.411 Hom.: 1868

Bravo AF: 0.349

Asia WGS AF: 0.338 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.53
PhyloP100		0.020
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: rs11237081; hg19: chr11-76794752;