rs11604536

chr11-77116314-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004055.5(CAPN5):c.971+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,607,764 control chromosomes in the GnomAD database, including 60,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7982 hom., cov: 33)
  • Exomes 𝑓: 0.26 (52578 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-77116314-A-G is Benign according to our data. Variant chr11-77116314-A-G is described in ClinVar as [Benign]. Clinvar id is 259225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN5	NM_004055.5	c.971+11A>G		intron_variant		ENST00000648180.1
CAPN5	XM_011545225.1	c.1091+11A>G		intron_variant
CAPN5	XM_017018223.3	c.1079+11A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN5	ENST00000648180.1	c.971+11A>G		intron_variant			NM_004055.5	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47001 AN: 151810 Hom.: 7958 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.284 AC: 69156 AN: 243598 Hom.: 10314 AF XY: 0.281 AC XY: 37039 AN XY: 131736

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.417

Gnomad SAS exome AF: 0.322

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.264 AC: 384135 AN: 1455834 Hom.: 52578 Cov.: 31 AF XY: 0.265 AC XY: 191904 AN XY: 723956

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.310 AC: 47084 AN: 151930 Hom.: 7982 Cov.: 33 AF XY: 0.308 AC XY: 22875 AN XY: 74248

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.289

Alfa AF: 0.287 Hom.: 2651

Bravo AF: 0.318

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	4.8
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs11604536; hg19: chr11-76827360; COSMIC: COSV53686697; COSMIC: COSV53686697;