Variant 11-77116314-A-G 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_004055.5(CAPN5):c.971+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,607,764 control chromosomes in the GnomAD database, including 60,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7982 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52578 hom. )

Consequence

CAPN5
NM_004055.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.80

Variant links:

Genes affected

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 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=-0.74).

BP6

Variant 11-77116314-A-G is Benign according to our data. Variant chr11-77116314-A-G is described in ClinVar as [Benign]. Clinvar id is 259225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CAPN5	NM_004055.5 linkuse as main transcript	c.971+11A>G	intron_variant	ENST00000648180.1	NP_004046.2	O15484A0A140VKH4
CAPN5	XM_011545225.1 linkuse as main transcript	c.1091+11A>G	intron_variant		XP_011543527.1
CAPN5	XM_017018223.3 linkuse as main transcript	c.1079+11A>G	intron_variant		XP_016873712.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1 linkuse as main transcript	c.971+11A>G		intron_variant			NM_004055.5	ENSP00000498132.1		O15484

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47001

AN:

151810

Hom.:

7958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.289

GnomAD3 exomes

AF:

0.284

AC:

69156

AN:

243598

Hom.:

10314

AF XY:

0.281

AC XY:

37039

AN XY:

131736

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.221

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.264

AC:

384135

AN:

1455834

Hom.:

52578

Cov.:

AF XY:

0.265

AC XY:

191904

AN XY:

723956

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.251

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.310

AC:

47084

AN:

151930

Hom.:

7982

Cov.:

AF XY:

0.308

AC XY:

22875

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.448

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.287

Hom.:

2651

Bravo

AF:

0.318

Asia WGS

AF:

0.346

AC:

1201

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

DANN

Benign

0.74

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