rs41266971

Positions:

• chr2-240591700-A-C
• chr2-240591700-A-T

Variant summary

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

The ENST00000391984.7(CAPN10):​c.471-233A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 567,468 control chromosomes in the GnomAD database, including 1,856 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 0.089 (691 hom., cov: 34)
  • Exomes 𝑓: 0.069 (1165 hom.)
• Consequence: CAPN10 ENST00000391984.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN10	NM_023083.4	c.471-233A>C		intron_variant		ENST00000391984.7	NP_075571.2
CAPN10	NM_023085.4	c.471-233A>C		intron_variant			NP_075573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7	c.471-233A>C		intron_variant		1	NM_023083.4	ENSP00000375844	P1

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13529 AN: 152176 Hom.: 688 Cov.: 34

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0765

GnomAD4 exome AF: 0.0691 AC: 28671 AN: 415174 Hom.: 1165 Cov.: 3 AF XY: 0.0685 AC XY: 14781 AN XY: 215638

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.0393

Gnomad4 ASJ exome AF: 0.0815

Gnomad4 EAS exome AF: 0.0194

Gnomad4 SAS exome AF: 0.0579

Gnomad4 FIN exome AF: 0.0989

Gnomad4 NFE exome AF: 0.0710

Gnomad4 OTH exome AF: 0.0724

GnomAD4 genome AF: 0.0889 AC: 13543 AN: 152294 Hom.: 691 Cov.: 34 AF XY: 0.0894 AC XY: 6659 AN XY: 74464

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0354 Hom.: 31

Bravo AF: 0.0864

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.49

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: rs41266971; hg19: chr2-241531117;