Genetic Variant CAPN14:p.Leu185Leu (chr2-31200622-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001145122.2(CAPN14):c.555C>T(p.Leu185Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,543,220 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

CAPN14
NM_001145122.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.486

Publications

1 publications found

Variant links:

Genes affected

CAPN14 (HGNC:16664): (calpain 14) Calpains are a family of cytosolic calcium-activated cysteine proteases involved in a variety of cellular processes including apoptosis, cell division, modulation of integrin-cytoskeletal interactions, and synaptic plasticity (Dear et al., 2000 [PubMed 10964513]). CAPN14 belongs to the calpain large subunit family.[supplied by OMIM, Mar 2008]

CAPN14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-31200622-G-A is Benign according to our data. Variant chr2-31200622-G-A is described in ClinVar as Benign. ClinVar VariationId is 780816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.486 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN14	NM_001145122.2 link	c.555C>T	p.Leu185Leu	synonymous_variant	Exon 6 of 22	ENST00000403897.4	NP_001138594.1	A8MX76-1B7Z467

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN14	ENST00000403897.4 link	c.555C>T	p.Leu185Leu	synonymous_variant	Exon 6 of 22	2	NM_001145122.2	ENSP00000385247.3		A8MX76-1
CAPN14	ENST00000398824.6 link	n.418C>T		non_coding_transcript_exon_variant	Exon 6 of 22	2		ENSP00000381805.2		F1LLU4

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00927

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000735

AC:

108

AN:

146896

AF XY:

0.000644

show subpopulations

Gnomad AFR exome

AF:

0.00980

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000209

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.000326

AC:

454

AN:

1390908

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

218

AN XY:

685666

show subpopulations

African (AFR)

AF:

0.00990

AC:

308

AN:

31108

American (AMR)

AF:

0.000540

AC:

AN:

33330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24632

East Asian (EAS)

AF:

0.00

AC:

AN:

35626

South Asian (SAS)

AF:

0.0000516

AC:

AN:

77506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49200

Middle Eastern (MID)

AF:

0.00213

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000613

AC:

AN:

1076262

Other (OTH)

AF:

0.000799

AC:

AN:

57600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00274

AC:

418

AN:

152312

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00929

AC:

386

AN:

41566

American (AMR)

AF:

0.00137

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68020

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00137

Hom.:

Bravo

AF:

0.00302

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.92

(source)

DANN

Benign

0.74

PhyloP100

-0.49

Mutation Taster

=99/1

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over