rs948976

Variant names:

• chr11-77074148-G-A
• rs948976
• NM_004055.5:c.-36+7054G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77074148-G-A
• chr11-77074148-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+7054G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,132 control chromosomes in the GnomAD database, including 41,268 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 0.73 (41268 hom., cov: 33)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.-36+7054G>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+7054G>A		intron_variant	Intron 1 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111561 AN: 152012 Hom.: 41221 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.734 AC: 111670 AN: 152132 Hom.: 41268 Cov.: 33 AF XY: 0.729 AC XY: 54219 AN XY: 74386

African (AFR) AF: 0.822 AC: 34113 AN: 41496

American (AMR) AF: 0.642 AC: 9822 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2583 AN: 3472

East Asian (EAS) AF: 0.626 AC: 3238 AN: 5172

South Asian (SAS) AF: 0.688 AC: 3313 AN: 4816

European-Finnish (FIN) AF: 0.724 AC: 7674 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48479 AN: 67968

Other (OTH) AF: 0.729 AC: 1541 AN: 2114

Alfa AF: 0.720 Hom.: 13221

Bravo AF: 0.733

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-0.99
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: rs948976; hg19: chr11-76785194; COSMIC: COSV53686681;