Variant 6-44172345-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007058.4(CAPN11):c.453C>T(p.Cys151Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,561,120 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 33 hom. )

Consequence

CAPN11
NM_007058.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.272

Variant links:

Genes affected

CAPN11 (HGNC:1478): (calpain 11) Calpains constitute a family of intracellular calcium-dependent cysteine proteases. There are eight members in this superfamily. They consist of a variable 80 kDa subunit and an invariant 30 kDa subunit. This calpain protein appears to have protease activity and calcium-binding ability. A similar mouse protein may play a functional role in spermatogenesis and in the regulation of calcium-dependent signal transduction events during meiosis. [provided by RefSeq, Dec 2008]

CAPN11 links:

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

POLR1C links:

CAPN11 (HGNC:):

CAPN11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-44172345-C-T is Benign according to our data. Variant chr6-44172345-C-T is described in ClinVar as [Benign]. Clinvar id is 778004.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.272 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN11	NM_007058.4 linkuse as main transcript	c.453C>T	p.Cys151Cys	synonymous_variant	5/23	ENST00000398776.2	NP_008989.2	Q9UMQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN11	ENST00000398776.2 linkuse as main transcript	c.453C>T	p.Cys151Cys	synonymous_variant	5/23	1	NM_007058.4	ENSP00000381758.1		Q9UMQ6
CAPN11	ENST00000532171.5 linkuse as main transcript	c.543C>T	p.Cys181Cys	synonymous_variant	6/6	4		ENSP00000432420.1		E9PQZ4

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00578

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00340

AC:

582

AN:

170960

Hom.:

AF XY:

0.00343

AC XY:

312

AN XY:

90888

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.000387

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00452

GnomAD4 exome

AF:

0.00590

AC:

8317

AN:

1408878

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

3939

AN XY:

695892

show subpopulations

Gnomad4 AFR exome

AF:

0.000784

Gnomad4 AMR exome

AF:

0.00457

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0000550

Gnomad4 SAS exome

AF:

0.000289

Gnomad4 FIN exome

AF:

0.000301

Gnomad4 NFE exome

AF:

0.00712

Gnomad4 OTH exome

AF:

0.00526

GnomAD4 genome

AF:

0.00382

AC:

582

AN:

152242

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

257

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00746

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00579

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.7

DANN

Benign

0.61

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