rs702466

Variant names:

• chr2-74142823-C-G
• rs702466
• NM_212552.3:c.170-463G>C

Variant summary

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

The NM_212552.3(BOLA3):​c.170-463G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,124 control chromosomes in the GnomAD database, including 9,425 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 0.33 (9425 hom., cov: 33)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 7 publications found

Genes affected

BOLA3 (HGNC:24415): (bolA family member 3) This gene encodes a protein that plays an essential role in the production of iron-sulfur (Fe-S) clusters for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases, and for the assembly of the mitochondrial respiratory chain complexes. Mutation in this gene has been associated with multiple mitochondrial dysfunctions syndrome-2. Two alternatively spliced transcript variants encoding different isoforms with distinct subcellular localization have been reported for this gene (PMID:21944046). [provided by RefSeq, Dec 2011]

BOLA3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple mitochondrial dysfunctions syndrome 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	NM_212552.3	MANE Select	c.170-463G>C		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.169+2366G>C		intron	N/A	NP_001030582.1	Q53S33-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	ENST00000327428.10	TSL:1 MANE Select	c.170-463G>C		intron	N/A	ENSP00000331369.5	Q53S33-1
	BOLA3	ENST00000295326.4	TSL:1	c.169+2366G>C		intron	N/A	ENSP00000295326.4	Q53S33-2
	BOLA3	ENST00000477685.5	TSL:1	n.321-463G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49738 AN: 152006 Hom.: 9423 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.327 AC: 49749 AN: 152124 Hom.: 9425 Cov.: 33 AF XY: 0.328 AC XY: 24408 AN XY: 74362

African (AFR) AF: 0.146 AC: 6060 AN: 41500

American (AMR) AF: 0.317 AC: 4844 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1403 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1156 AN: 5174

South Asian (SAS) AF: 0.216 AC: 1038 AN: 4816

European-Finnish (FIN) AF: 0.524 AC: 5533 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28522 AN: 67994

Other (OTH) AF: 0.350 AC: 741 AN: 2116

Alfa AF: 0.376 Hom.: 1494

Bravo AF: 0.305

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.43
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: rs702466; hg19: chr2-74369950;