rs3792267

chr2-240591757-G-A

Variant summary

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

The NM_023083.4(CAPN10):c.471-176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 615,740 control chromosomes in the GnomAD database, including 18,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4176 hom., cov: 34)
  • Exomes 𝑓: 0.24 (14776 hom.)
• Consequence: CAPN10 NM_023083.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -3.50

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN10	NM_023083.4	c.471-176G>A		intron_variant		ENST00000391984.7
CAPN10	NM_023085.4	c.471-176G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN10	ENST00000391984.7	c.471-176G>A		intron_variant		1	NM_023083.4	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34251 AN: 152182 Hom.: 4171 Cov.: 34

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.244 AC: 113000 AN: 463440 Hom.: 14776 Cov.: 5 AF XY: 0.243 AC XY: 58841 AN XY: 242506

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.0707

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.225 AC: 34270 AN: 152300 Hom.: 4176 Cov.: 34 AF XY: 0.223 AC XY: 16570 AN XY: 74468

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0811

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.228

Alfa AF: 0.262 Hom.: 6558

Bravo AF: 0.224

Asia WGS AF: 0.131 AC: 454 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus 1, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.052
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3792267; hg19: chr2-241531174;