rs4945140

Variant names:

• chr11-77074406-G-A
• rs4945140
• NM_004055.5:c.-36+7312G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77074406-G-A
• chr11-77074406-G-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.-36+7312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,606 control chromosomes in the GnomAD database, including 11,232 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 0.36 (11232 hom., cov: 32)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.-36+7312G>A		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.-36+7312G>A		intron_variant	Intron 1 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55306 AN: 151484 Hom.: 11231 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.365 AC: 55319 AN: 151606 Hom.: 11232 Cov.: 32 AF XY: 0.365 AC XY: 27049 AN XY: 74062

African (AFR) AF: 0.192 AC: 7899 AN: 41186

American (AMR) AF: 0.340 AC: 5185 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1088 AN: 5144

South Asian (SAS) AF: 0.437 AC: 2098 AN: 4796

European-Finnish (FIN) AF: 0.504 AC: 5308 AN: 10536

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30785 AN: 67922

Other (OTH) AF: 0.367 AC: 773 AN: 2104

Alfa AF: 0.386 Hom.: 4312

Bravo AF: 0.344

Asia WGS AF: 0.329 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.60
PhyloP100		-0.94
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: rs4945140; hg19: chr11-76785452;