Variant chrX-111247263-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014289.4(CAPN6):c.1743+105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 752,322 control chromosomes in the GnomAD database, including 3,934 homozygotes. There are 10,383 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2274 hom., 4018 hem., cov: 21)

Exomes 𝑓: 0.041 ( 1660 hom. 6365 hem. )

Consequence

CAPN6
NM_014289.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.761

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-111247263-C-T is Benign according to our data. Variant chrX-111247263-C-T is described in ClinVar as [Benign]. Clinvar id is 1179669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 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.1743+105G>A		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.1743+105G>A		intron_variant		1	NM_014289.4	ENSP00000317214.1		Q9Y6Q1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

15810

AN:

108599

Hom.:

2273

Cov.:

AF XY:

0.128

AC XY:

3990

AN XY:

31115

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.00593

Gnomad AMR

AF:

0.0794

Gnomad ASJ

AF:

0.0192

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00972

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.113

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.0406

AC:

26147

AN:

643675

Hom.:

1660

AF XY:

0.0407

AC XY:

6365

AN XY:

156251

show subpopulations

Gnomad4 AFR exome

AF:

0.458

Gnomad4 AMR exome

AF:

0.0499

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.000531

Gnomad4 SAS exome

AF:

0.00964

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0616

GnomAD4 genome

AF:

0.146

AC:

15841

AN:

108647

Hom.:

2274

Cov.:

AF XY:

0.129

AC XY:

4018

AN XY:

31173

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.0792

Gnomad4 ASJ

AF:

0.0192

Gnomad4 EAS

AF:

0.00115

Gnomad4 SAS

AF:

0.00895

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0307

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0448

Hom.:

258

Bravo

AF:

0.166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.40

DANN

Benign

0.51

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