NM_004055.5:c.298-151C>T

Variant names:

• chr11-77112438-C-T
• rs3781684
• NM_004055.5:c.298-151C>T

Variant summary

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

The NM_004055.5(CAPN5):​c.298-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 652,574 control chromosomes in the GnomAD database, including 3,458 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 0.084 (702 hom., cov: 32)
  • Exomes 𝑓: 0.087 (2756 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004055.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN5	NM_004055.5	MANE Select	c.298-151C>T		intron	N/A	NP_004046.2
	CAPN5	NM_001425321.1		c.418-151C>T		intron	N/A	NP_001412250.1
	CAPN5	NM_001425322.1		c.298-151C>T		intron	N/A	NP_001412251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN5	ENST00000648180.1	MANE Select	c.298-151C>T		intron	N/A	ENSP00000498132.1
	CAPN5	ENST00000529629.5	TSL:1	c.298-151C>T		intron	N/A	ENSP00000432332.1
	CAPN5	ENST00000886046.1		c.526-151C>T		intron	N/A	ENSP00000556105.1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12696 AN: 152036 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0871 AC: 43586 AN: 500420 Hom.: 2756 AF XY: 0.0901 AC XY: 23737 AN XY: 263510

African (AFR) AF: 0.102 AC: 1448 AN: 14224

American (AMR) AF: 0.0905 AC: 2474 AN: 27342

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 723 AN: 15372

East Asian (EAS) AF: 0.259 AC: 8168 AN: 31516

South Asian (SAS) AF: 0.154 AC: 7678 AN: 49892

European-Finnish (FIN) AF: 0.0529 AC: 1679 AN: 31752

Middle Eastern (MID) AF: 0.0930 AC: 198 AN: 2130

European-Non Finnish (NFE) AF: 0.0634 AC: 19022 AN: 300176

Other (OTH) AF: 0.0784 AC: 2196 AN: 28016

GnomAD4 genome AF: 0.0835 AC: 12712 AN: 152154 Hom.: 702 Cov.: 32 AF XY: 0.0845 AC XY: 6282 AN XY: 74376

African (AFR) AF: 0.101 AC: 4175 AN: 41492

American (AMR) AF: 0.0715 AC: 1094 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5162

South Asian (SAS) AF: 0.151 AC: 725 AN: 4808

European-Finnish (FIN) AF: 0.0552 AC: 586 AN: 10608

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0629 AC: 4278 AN: 67994

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0737 Hom.: 1757

Bravo AF: 0.0858

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		-0.34
PromoterAI		-0.093	Neutral
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: rs3781684; hg19: chr11-76823484; COSMIC: COSV53687636;