rs7102149

Positions:

• chr11-77088177-G-A

Variant summary

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

The NM_004055.5(CAPN5):​c.165+3126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,033,198 control chromosomes in the GnomAD database, including 56,987 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 0.30 (7211 hom., cov: 29)
  • Exomes 𝑓: 0.31 (49776 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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 = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN5	NM_004055.5	c.165+3126G>A		intron_variant		ENST00000648180.1
CAPN5	XM_011545225.1	c.285+3126G>A		intron_variant
CAPN5	XM_017018223.3	c.273+3126G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN5	ENST00000648180.1	c.165+3126G>A		intron_variant			NM_004055.5	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44947 AN: 151462 Hom.: 7209 Cov.: 29

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.313 AC: 275785 AN: 881618 Hom.: 49776 AF XY: 0.312 AC XY: 137228 AN XY: 439404

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.297 AC: 44969 AN: 151580 Hom.: 7211 Cov.: 29 AF XY: 0.294 AC XY: 21718 AN XY: 73992

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.340

Alfa AF: 0.339 Hom.: 1846

Bravo AF: 0.292

Asia WGS AF: 0.277 AC: 963 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	0.68
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7102149; hg19: chr11-76799223;