Variant rs926412 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014289.4(CAPN6):c.1158+128A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 633,511 control chromosomes in the GnomAD database, including 1,577 homozygotes. There are 4,628 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.088 ( 1024 hom., 2592 hem., cov: 22)

Exomes 𝑓: 0.015 ( 553 hom. 2036 hem. )

Consequence

CAPN6
NM_014289.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.207

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-111250789-T-A is Benign according to our data. Variant chrX-111250789-T-A is described in ClinVar as [Benign]. Clinvar id is 1225678.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPN6	NM_014289.4 linkuse as main transcript	c.1158+128A>T		intron_variant		ENST00000324068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN6	ENST00000324068.2 linkuse as main transcript	c.1158+128A>T		intron_variant		1	NM_014289.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0879

AC:

9816

AN:

111705

Hom.:

1024

Cov.:

AF XY:

0.0762

AC XY:

2584

AN XY:

33917

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.00756

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000652

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00580

Gnomad OTH

AF:

0.0657

GnomAD4 exome

AF:

0.0147

AC:

7688

AN:

521754

Hom.:

553

AF XY:

0.0136

AC XY:

2036

AN XY:

149718

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.0257

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.0000367

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.00498

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0879

AC:

9826

AN:

111757

Hom.:

1024

Cov.:

AF XY:

0.0763

AC XY:

2592

AN XY:

33979

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.0483

Gnomad4 ASJ

AF:

0.00756

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00112

Gnomad4 FIN

AF:

0.000652

Gnomad4 NFE

AF:

0.00580

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0555

Hom.:

295

Bravo

AF:

0.104

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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

DANN

Benign

0.55

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