Variant rs2953171 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023083.4(CAPN10):c.1482-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,528,980 control chromosomes in the GnomAD database, including 24,785 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 0.17 ( 2319 hom., cov: 34)

Exomes 𝑓: 0.18 ( 22466 hom. )

Consequence

CAPN10
NM_023083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.608

Variant links:

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]

CAPN10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN10	NM_023083.4 linkuse as main transcript	c.1482-45C>T		intron_variant		ENST00000391984.7	NP_075571.2
CAPN10	NM_023085.4 linkuse as main transcript	c.1279-1252C>T		intron_variant			NP_075573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7 linkuse as main transcript	c.1482-45C>T		intron_variant		1	NM_023083.4	ENSP00000375844	P1	Q9HC96-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25451

AN:

152134

Hom.:

2323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.194

AC:

34865

AN:

179982

Hom.:

3583

AF XY:

0.191

AC XY:

18305

AN XY:

95946

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.0976

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.177

AC:

243797

AN:

1376728

Hom.:

22466

Cov.:

AF XY:

0.177

AC XY:

119267

AN XY:

675466

show subpopulations

Gnomad4 AFR exome

AF:

0.113

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.0956

Gnomad4 EAS exome

AF:

0.308

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.167

AC:

25458

AN:

152252

Hom.:

2319

Cov.:

AF XY:

0.172

AC XY:

12817

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.0878

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.162

Hom.:

276

Bravo

AF:

0.165

Asia WGS

AF:

0.246

AC:

857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over