chr2-74135863-T-A

Position:

• chr2-74135863-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_212552.3(BOLA3):​c.259-205A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,990 control chromosomes in the GnomAD database, including 4,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4442 hom., cov: 32)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-74135863-T-A is Benign according to our data. Variant chr2-74135863-T-A is described in ClinVar as [Benign]. Clinvar id is 669781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BOLA3	NM_212552.3	c.259-205A>T		intron_variant		ENST00000327428.10	NP_997717.2
BOLA3	NM_001035505.2	c.170-205A>T		intron_variant			NP_001030582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BOLA3	ENST00000327428.10	c.259-205A>T		intron_variant		1	NM_212552.3	ENSP00000331369	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33704 AN: 151872 Hom.: 4430 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.222 AC: 33748 AN: 151990 Hom.: 4442 Cov.: 32 AF XY: 0.226 AC XY: 16816 AN XY: 74280

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.234

Alfa AF: 0.184 Hom.: 426

Bravo AF: 0.246

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 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
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.70
DANN	Benign	0.40

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: rs9789534; hg19: chr2-74362990;