2-74142823-C-G

Position:

• chr2-74142823-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOLA3	NM_212552.3	c.170-463G>C		intron_variant		ENST00000327428.10
BOLA3	NM_001035505.2	c.169+2366G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOLA3	ENST00000327428.10	c.170-463G>C		intron_variant		1	NM_212552.3	P1

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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.350

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.58

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: rs702466; hg19: chr2-74369950;