Variant 2-31191964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001145122.2(CAPN14):c.1249C>T(p.Leu417Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,551,466 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 69 hom. )

Consequence

CAPN14
NM_001145122.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.944

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038277209).

BP6

Variant 2-31191964-G-A is Benign according to our data. Variant chr2-31191964-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 717612.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN14	NM_001145122.2 linkuse as main transcript	c.1249C>T	p.Leu417Phe	missense_variant	11/22	ENST00000403897.4	NP_001138594.1	A8MX76-1B7Z467

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPN14	ENST00000403897.4 linkuse as main transcript	c.1249C>T	p.Leu417Phe	missense_variant	11/22	2	NM_001145122.2	ENSP00000385247.3	A8MX76-1
CAPN14	ENST00000398824.6 linkuse as main transcript	n.*680C>T		non_coding_transcript_exon_variant	11/22	2		ENSP00000381805.2	F1LLU4
CAPN14	ENST00000398824.6 linkuse as main transcript	n.*680C>T		3_prime_UTR_variant	11/22	2		ENSP00000381805.2	F1LLU4

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

994

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00732

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00636

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00749

AC:

1155

AN:

154224

Hom.:

AF XY:

0.00722

AC XY:

591

AN XY:

81854

show subpopulations

Gnomad AFR exome

AF:

0.000761

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.000236

Gnomad EAS exome

AF:

0.00734

Gnomad SAS exome

AF:

0.00158

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.00527

Gnomad OTH exome

AF:

0.00644

GnomAD4 exome

AF:

0.00611

AC:

8555

AN:

1399116

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

4104

AN XY:

690044

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.00308

Gnomad4 SAS exome

AF:

0.00163

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00531

GnomAD4 genome

AF:

0.00652

AC:

993

AN:

152350

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

561

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00714

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.00636

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.00385

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00503

AC:

ExAC

AF:

0.00513

AC:

126

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

case-control

UM ALS/MND Lab, University Of Malta

Sep 09, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.3

DANN

Benign

0.91

DEOGEN2

Benign

0.11

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.11

MVP

0.030

ClinPred

0.0016

GERP RS

1.9

Varity_R

0.069

gMVP

0.27

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