Variant X-111251300-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014289.4(CAPN6):c.894-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 2090 hom., 2243 hem., cov: 18)

Exomes 𝑓: 0.16 ( 124 hom. 374 hem. )

Consequence

CAPN6
NM_014289.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

CAPN6 (HGNC:1483): (calpain 6) Calpains are 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 subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis. [provided by RefSeq, Nov 2009]

CAPN6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-111251300-G-GA is Benign according to our data. Variant chrX-111251300-G-GA is described in ClinVar as [Benign]. Clinvar id is 1250758.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN6	NM_014289.4 linkuse as main transcript	c.894-15dupT		intron_variant		ENST00000324068.2	NP_055104.2	Q9Y6Q1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN6	ENST00000324068.2 linkuse as main transcript	c.894-15dupT		intron_variant		1	NM_014289.4	ENSP00000317214.1		Q9Y6Q1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

12284

AN:

85624

Hom.:

2087

Cov.:

AF XY:

0.110

AC XY:

2236

AN XY:

20384

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0750

Gnomad ASJ

AF:

0.00854

Gnomad EAS

AF:

0.00109

Gnomad SAS

AF:

0.00690

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.0741

Gnomad NFE

AF:

0.00906

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.234

AC:

10592

AN:

45184

Hom.:

AF XY:

0.0260

AC XY:

AN XY:

2042

show subpopulations

Gnomad AFR exome

AF:

0.430

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.156

AC:

97323

AN:

622828

Hom.:

124

Cov.:

AF XY:

0.00253

AC XY:

374

AN XY:

147590

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.144

AC:

12295

AN:

85620

Hom.:

2090

Cov.:

AF XY:

0.110

AC XY:

2243

AN XY:

20396

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.00854

Gnomad4 EAS

AF:

0.00109

Gnomad4 SAS

AF:

0.00588

Gnomad4 FIN

AF:

0.00773

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over