rs10501410

Positions:

• chr11-72377762-G-A
• chr11-72377762-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258392.3(CLPB):​c.646+2519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,030 control chromosomes in the GnomAD database, including 2,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2285 hom., cov: 31)
• Consequence: CLPB NM_001258392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPB	NM_030813.6	c.646+2519C>T		intron_variant		ENST00000294053.9	NP_110440.1
CLPB	NM_001258392.3	c.646+2519C>T		intron_variant		ENST00000538039.6	NP_001245321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPB	ENST00000294053.9	c.646+2519C>T		intron_variant		1	NM_030813.6	ENSP00000294053.3
CLPB	ENST00000538039.6	c.646+2519C>T		intron_variant		2	NM_001258392.3	ENSP00000441518.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21127 AN: 151914 Hom.: 2261 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.139 AC: 21195 AN: 152030 Hom.: 2285 Cov.: 31 AF XY: 0.137 AC XY: 10202 AN XY: 74326

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.0711

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0719 Hom.: 524

Bravo AF: 0.144

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs10501410; hg19: chr11-72088806;