11-77112438-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001425321.1(CAPN5):​c.418-151C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 500,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: CAPN5 NM_001425321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425321.1. 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>G		intron	N/A	NP_004046.2
	CAPN5	NM_001425321.1		c.418-151C>G		intron	N/A	NP_001412250.1
	CAPN5	NM_001425322.1		c.298-151C>G		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>G		intron	N/A	ENSP00000498132.1
	CAPN5	ENST00000529629.5	TSL:1	c.298-151C>G		intron	N/A	ENSP00000432332.1
	CAPN5	ENST00000886046.1		c.526-151C>G		intron	N/A	ENSP00000556105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000200 AC: 1 AN: 500538 Hom.: 0 AF XY: 0.00000379 AC XY: 1 AN XY: 263564

African (AFR) AF: 0.00 AC: 0 AN: 14232

American (AMR) AF: 0.00 AC: 0 AN: 27350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15372

East Asian (EAS) AF: 0.00 AC: 0 AN: 31526

South Asian (SAS) AF: 0.00 AC: 0 AN: 49904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2130

European-Non Finnish (NFE) AF: 0.00000333 AC: 1 AN: 300242

Other (OTH) AF: 0.00 AC: 0 AN: 28026

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.45
PhyloP100		-0.34
PromoterAI		-0.11	Neutral

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;