11-72308597-C-T

Position:

chr11-72308597-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_030813.6(CLPB):c.1086G>A(p.Arg362=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,614,034 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 74 hom. )

Consequence

CLPB
NM_030813.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

CLPB (HGNC:30664): (ClpB family mitochondrial disaggregase) This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

CLPB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 11-72308597-C-T is Benign according to our data. Variant chr11-72308597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00729 (1110/152290) while in subpopulation NFE AF= 0.0101 (686/68018). AF 95% confidence interval is 0.00946. There are 4 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPB	NM_030813.6 linkuse as main transcript	c.1086G>A	p.Arg362=	synonymous_variant	9/17	ENST00000294053.9
CLPB	NM_001258392.3 linkuse as main transcript	c.996G>A	p.Arg332=	synonymous_variant	8/16	ENST00000538039.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPB	ENST00000294053.9 linkuse as main transcript	c.1086G>A	p.Arg362=	synonymous_variant	9/17	1	NM_030813.6	P4	Q9H078-1
CLPB	ENST00000538039.6 linkuse as main transcript	c.996G>A	p.Arg332=	synonymous_variant	8/16	2	NM_001258392.3	A1	Q9H078-2

Frequencies

GnomAD3 genomes

AF:

0.00730

AC:

1111

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00753

AC:

1893

AN:

251464

Hom.:

AF XY:

0.00760

AC XY:

1033

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00844

AC:

12343

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

6085

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.0207

Gnomad4 NFE exome

AF:

0.00930

Gnomad4 OTH exome

AF:

0.00737

GnomAD4 genome

AF:

0.00729

AC:

1110

AN:

152290

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

560

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00663

Hom.:

Bravo

AF:

0.00558

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00894

EpiControl

AF:

0.00848

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CLPB: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 15, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

3-methylglutaconic aciduria, type VIIB

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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