11-77081385-C-A

Variant names:

• chr11-77081385-C-A
• rs7926553
• NM_004055.5:c.-35-3467C>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.-35-3467C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,038 control chromosomes in the GnomAD database, including 21,741 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 0.52 (21741 hom., cov: 32)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 11 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 = 0.613 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN5	NM_004055.5	MANE Select	c.-35-3467C>A		intron	N/A	NP_004046.2
	CAPN5	NM_001425321.1		c.-35-3467C>A		intron	N/A	NP_001412250.1
	CAPN5	NM_001425322.1		c.-35-3467C>A		intron	N/A	NP_001412251.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN5	ENST00000648180.1	MANE Select	c.-35-3467C>A		intron	N/A	ENSP00000498132.1
	CAPN5	ENST00000529629.5	TSL:1	c.-35-3467C>A		intron	N/A	ENSP00000432332.1
	CAPN5	ENST00000456580.6	TSL:2	c.-35-3467C>A		intron	N/A	ENSP00000409996.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78822 AN: 151920 Hom.: 21738 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.519 AC: 78858 AN: 152038 Hom.: 21741 Cov.: 32 AF XY: 0.518 AC XY: 38468 AN XY: 74272

African (AFR) AF: 0.322 AC: 13359 AN: 41466

American (AMR) AF: 0.481 AC: 7354 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2235 AN: 5158

South Asian (SAS) AF: 0.554 AC: 2662 AN: 4808

European-Finnish (FIN) AF: 0.657 AC: 6944 AN: 10574

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41994 AN: 67968

Other (OTH) AF: 0.543 AC: 1145 AN: 2108

Alfa AF: 0.585 Hom.: 86337

Bravo AF: 0.498

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		-0.090
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: rs7926553; hg19: chr11-76792431;