rs7943320

Variant names:

• chr11-77096039-G-A
• rs7943320
• NM_004055.5:c.297+2226G>A

Variant summary

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

The NM_004055.5(CAPN5):​c.297+2226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 152,236 control chromosomes in the GnomAD database, including 63 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 0.015 (63 hom., cov: 33)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.297+2226G>A		intron_variant	Intron 3 of 12	ENST00000648180.1	NP_004046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.297+2226G>A		intron_variant	Intron 3 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2294 AN: 152118 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00907

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

GnomAD4 genome AF: 0.0152 AC: 2310 AN: 152236 Hom.: 63 Cov.: 33 AF XY: 0.0148 AC XY: 1099 AN XY: 74406

African (AFR) AF: 0.0532 AC: 2210 AN: 41514

American (AMR) AF: 0.00399 AC: 61 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4816

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.0160 Hom.: 30

Bravo AF: 0.0165

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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: rs7943320; hg19: chr11-76807085;