Variant rs545353866 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_006012.4(CLPP):c.-7_-6insCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,397,388 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

CLPP
NM_006012.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.590

Variant links:

Genes affected

CLPP (HGNC:2084): (caseinolytic mitochondrial matrix peptidase proteolytic subunit) The protein encoded by this gene belongs to the peptidase family S14 and hydrolyzes proteins into small peptides in the presence of ATP and magnesium. The protein is transported into mitochondrial matrix and is associated with the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]

CLPP links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-6361567-G-GCC is Benign according to our data. Variant chr19-6361567-G-GCC is described in ClinVar as [Likely_benign]. Clinvar id is 504858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00144 (220/152354) while in subpopulation NFE AF= 0.00218 (148/68040). AF 95% confidence interval is 0.00189. There are 2 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPP	NM_006012.4 linkuse as main transcript	c.-7_-6insCC		5_prime_UTR_variant	1/6	ENST00000245816.11	NP_006003.1
CLPP	XM_047439486.1 linkuse as main transcript	c.-7_-6insCC		5_prime_UTR_variant	1/5		XP_047295442.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
CLPP	ENST00000245816.11 linkuse as main transcript	c.-7_-6insCC	5_prime_UTR_variant	1/6	1	NM_006012.4	ENSP00000245816	P1
	ENST00000595644.1 linkuse as main transcript	n.35+547_35+548insGG	intron_variant, non_coding_transcript_variant		4
CLPP	ENST00000596070.1 linkuse as main transcript	n.4_5insCC	non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00217

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00140

AC:

AN:

46530

Hom.:

AF XY:

0.00133

AC XY:

AN XY:

23262

show subpopulations

Gnomad AFR exome

AF:

0.000444

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00523

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00104

Gnomad FIN exome

AF:

0.000400

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.000954

GnomAD4 exome

AF:

0.00184

AC:

2297

AN:

1245034

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1159

AN XY:

600774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000831

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00576

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000528

Gnomad4 FIN exome

AF:

0.000587

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00198

GnomAD4 genome

AF:

0.00144

AC:

220

AN:

152354

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00218

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.00148

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 20, 2016	c.-7_-6insCC in exon 1 of CLPP: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (19/2910) of European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs545353866). -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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