dbSNP rs11604536: CAPN5:c.971+11A>G (chr11-77116314-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

CAPN5-related vitreoretinopathy
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
autosomal dominant neovascular inflammatory vitreoretinopathy
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

CAPN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004055.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAPN5	NM_004055.5	MANE Select	c.971+11A>G	intron	N/A	NP_004046.2
CAPN5	NM_001425321.1		c.1091+11A>G	intron	N/A	NP_001412250.1	E7EV01
CAPN5	NM_001425322.1		c.971+11A>G	intron	N/A	NP_001412251.1	A0A140VKH4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAPN5	ENST00000648180.1	MANE Select	c.971+11A>G	intron	N/A	ENSP00000498132.1	O15484
CAPN5	ENST00000529629.5	TSL:1	c.971+11A>G	intron	N/A	ENSP00000432332.1	O15484
CAPN5	ENST00000886046.1		c.1199+11A>G	intron	N/A	ENSP00000556105.1

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

GnomAD2 exomes

AF:

0.284

AC:

69156

AN:

243598

AF XY:

0.281

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 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

African (AFR)

AF:

0.459

AC:

15306

AN:

33370

American (AMR)

AF:

0.279

AC:

12354

AN:

44260

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4312

AN:

26082

East Asian (EAS)

AF:

0.426

AC:

16871

AN:

39558

South Asian (SAS)

AF:

0.322

AC:

27477

AN:

85422

European-Finnish (FIN)

AF:

0.223

AC:

11873

AN:

53186

Middle Eastern (MID)

AF:

0.271

AC:

1560

AN:

5746

European-Non Finnish (NFE)

AF:

0.251

AC:

278250

AN:

1108044

Other (OTH)

AF:

0.268

AC:

16132

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13733

27467

41200

54934

68667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9560

19120

28680

38240

47800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

47084

AN:

151930

Hom.:

7982

Cov.:

AF XY:

0.308

AC XY:

22875

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.448

AC:

18525

AN:

41394

American (AMR)

AF:

0.250

AC:

3820

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

569

AN:

3466

East Asian (EAS)

AF:

0.432

AC:

2217

AN:

5136

South Asian (SAS)

AF:

0.311

AC:

1500

AN:

4820

European-Finnish (FIN)

AF:

0.225

AC:

2383

AN:

10594

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17218

AN:

67920

Other (OTH)

AF:

0.289

AC:

610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1617

3235

4852

6470

8087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.287

Hom.:

2651

Bravo

AF:

0.318

Asia WGS

AF:

0.346

AC:

1201

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

(source)

DANN

Benign

0.74

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over