rs10501410

Variant names:

• chr11-72377762-G-A
• rs10501410
• NM_030813.6:c.646+2519C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030813.6(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_030813.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• 3-methylglutaconic aciduria, type VIIB

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neutropenia, severe congenital, 9, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLPB	NM_030813.6	c.646+2519C>T		intron_variant	Intron 4 of 16	ENST00000294053.9	NP_110440.1
CLPB	NM_001258392.3	c.646+2519C>T		intron_variant	Intron 4 of 15	ENST00000538039.6	NP_001245321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPB	ENST00000294053.9	c.646+2519C>T		intron_variant	Intron 4 of 16	1	NM_030813.6	ENSP00000294053.3
CLPB	ENST00000538039.6	c.646+2519C>T		intron_variant	Intron 4 of 15	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

African (AFR) AF: 0.307 AC: 12711 AN: 41368

American (AMR) AF: 0.0711 AC: 1086 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.134 AC: 692 AN: 5180

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10598

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0693 AC: 4714 AN: 67990

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0828 Hom.: 1051

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
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10501410; hg19: chr11-72088806;