chr11-77112438-C-T

Position:

• chr11-77112438-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004055.5(CAPN5):​c.298-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 652,574 control chromosomes in the GnomAD database, including 3,458 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 0.084 (702 hom., cov: 32)
  • Exomes 𝑓: 0.087 (2756 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN5	NM_004055.5	c.298-151C>T		intron_variant		ENST00000648180.1
CAPN5	XM_011545225.1	c.418-151C>T		intron_variant
CAPN5	XM_017018223.3	c.406-151C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN5	ENST00000648180.1	c.298-151C>T		intron_variant			NM_004055.5	P1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12696 AN: 152036 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0871 AC: 43586 AN: 500420 Hom.: 2756 AF XY: 0.0901 AC XY: 23737 AN XY: 263510

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0905

Gnomad4 ASJ exome AF: 0.0470

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0529

Gnomad4 NFE exome AF: 0.0634

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.0835 AC: 12712 AN: 152154 Hom.: 702 Cov.: 32 AF XY: 0.0845 AC XY: 6282 AN XY: 74376

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0552

Gnomad4 NFE AF: 0.0629

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0713 Hom.: 1043

Bravo AF: 0.0858

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.75

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: rs3781684; hg19: chr11-76823484; COSMIC: COSV53687636;