2-74135948-C-CTTT

Position:

• chr2-74135948-C-CTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_212552.3(BOLA3):​c.259-291_259-290insAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0078 (20 hom., cov: 0)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489

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 -10 ACMG points.

• BP6: Variant 2-74135948-C-CTTT is Benign according to our data. Variant chr2-74135948-C-CTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1220343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00776 (1045/134678) while in subpopulation AMR AF= 0.0305 (399/13076). AF 95% confidence interval is 0.028. There are 20 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BOLA3	NM_212552.3	c.259-291_259-290insAAA		intron_variant		ENST00000327428.10	NP_997717.2
BOLA3	NM_001035505.2	c.170-291_170-290insAAA		intron_variant			NP_001030582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BOLA3	ENST00000327428.10	c.259-291_259-290insAAA		intron_variant		1	NM_212552.3	ENSP00000331369	P1

Frequencies

GnomAD3 genomes AF: 0.00774 AC: 1043 AN: 134694 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.00165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.00242

Gnomad EAS AF: 0.000430

Gnomad SAS AF: 0.00169

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00734

Gnomad OTH AF: 0.00926

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

GnomAD4 genome AF: 0.00776 AC: 1045 AN: 134678 Hom.: 20 Cov.: 0 AF XY: 0.00820 AC XY: 527 AN XY: 64298

Gnomad4 AFR AF: 0.00165

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.00242

Gnomad4 EAS AF: 0.000431

Gnomad4 SAS AF: 0.00170

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00734

Gnomad4 OTH AF: 0.00923

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55654893; hg19: chr2-74363075;