rs12039801

Positions:

• chr1-228181911-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010867.4(IBA57):​c.*6398G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 152,360 control chromosomes in the GnomAD database, including 193 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 0.047 (193 hom., cov: 32)
  • Exomes 𝑓: 0.077 (0 hom.)
• Consequence: IBA57 NM_001010867.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

Genes affected

IBA57 (HGNC:27302): (iron-sulfur cluster assembly factor IBA57) The protein encoded by this gene localizes to the mitochondrion and is part of the iron-sulfur cluster assembly pathway. The encoded protein functions late in the biosynthesis of mitochondrial 4Fe-4S proteins. Defects in this gene have been associated with autosomal recessive spastic paraplegia-74 and with multiple mitochondrial dysfunctions syndrome-3. Two transcript variants encoding different isoforms have been found for this gene. The smaller isoform is not likely to be localized to the mitochondrion since it lacks the amino-terminal transit peptide. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IBA57	NM_001010867.4	c.*6398G>A		3_prime_UTR_variant	3/3	ENST00000366711.4	NP_001010867.1
IBA57	NM_001310327.2	c.*6398G>A		3_prime_UTR_variant	3/3		NP_001297256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IBA57	ENST00000366711.4	c.*6398G>A		3_prime_UTR_variant	3/3	2	NM_001010867.4	ENSP00000355672	P1
IBA57	ENST00000484749.5	n.9469G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7112 AN: 152216 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0769 AC: 2 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0466 AC: 7105 AN: 152334 Hom.: 193 Cov.: 32 AF XY: 0.0477 AC XY: 3552 AN XY: 74498

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0441 Hom.: 32

Bravo AF: 0.0470

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs12039801; hg19: chr1-228369612;