Variant chr19-36146302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001749.4(CAPNS1):c.711C>T(p.Asp237Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,609,430 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 14 hom. )

Consequence

CAPNS1
NM_001749.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

CAPNS1 (HGNC:1481): (calpain small subunit 1) This gene is a member of the calpain small subunit family. Calpains are calcium-dependent cysteine proteinases that are widely distributed in mammalian cells. Calpains operate as heterodimers, comprising a specific large catalytic subunit (calpain 1 subunit in Calpain I, and calpain 2 subunit in Calpain II), and a common small regulatory subunit encoded by this gene. This encoded protein is essential for the stability and function of both calpain heterodimers, whose proteolytic activities influence various cellular functions including apoptosis, proliferation, migration, adhesion, and autophagy. Calpains have been implicated in neurodegenerative processes, such as myotonic dystrophy. A pseudogene of this gene has been defined on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

CAPNS1 links:

CAPNS1 (HGNC:):

CAPNS1 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 (BayesDel_noAF=-0.4).

BP6

Variant 19-36146302-C-T is Benign according to our data. Variant chr19-36146302-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024742.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPNS1	NM_001749.4 linkuse as main transcript	c.711C>T	p.Asp237Asp	synonymous_variant	9/11	ENST00000246533.8	NP_001740.1	P04632

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPNS1	ENST00000246533.8 linkuse as main transcript	c.711C>T	p.Asp237Asp	synonymous_variant	9/11	1	NM_001749.4	ENSP00000246533.2		P04632

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00305

AC:

768

AN:

251456

Hom.:

AF XY:

0.00316

AC XY:

430

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00281

AC:

4092

AN:

1457086

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

2085

AN XY:

725206

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00924

Gnomad4 EAS exome

AF:

0.000983

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00764

Gnomad4 NFE exome

AF:

0.00284

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00284

AC:

432

AN:

152344

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00433

Hom.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CAPNS1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.3

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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