chr11-77081385-C-A

Position:

• chr11-77081385-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.-35-3467C>A		intron_variant		ENST00000648180.1	NP_004046.2
CAPN5	XM_011545225.1	c.86-3467C>A		intron_variant			XP_011543527.1
CAPN5	XM_017018223.3	c.74-3467C>A		intron_variant			XP_016873712.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.-35-3467C>A		intron_variant			NM_004055.5	ENSP00000498132	P1

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.543

Alfa AF: 0.601 Hom.: 28802

Bravo AF: 0.498

Asia WGS AF: 0.497 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.68

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: rs7926553; hg19: chr11-76792431;