1-246542837-C-T

Variant summary

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

The NM_022366.3(TFB2M):c.1020-1635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 150,792 control chromosomes in the GnomAD database, including 4,856 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 0.24 (4856 hom., cov: 31)
• Consequence: TFB2M NM_022366.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

Genes affected

TFB2M (HGNC:18559): (transcription factor B2, mitochondrial) Enables mitochondrial transcription factor activity. Involved in transcription initiation from mitochondrial promoter. Located in mitochondrial nucleoid. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFB2M	NM_022366.3	c.1020-1635G>A		intron_variant		ENST00000366514.5
TFB2M	XM_011544248.2	c.717-1635G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFB2M	ENST00000366514.5	c.1020-1635G>A		intron_variant		1	NM_022366.3	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36489 AN: 150734 Hom.: 4857 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.242 AC: 36495 AN: 150792 Hom.: 4856 Cov.: 31 AF XY: 0.237 AC XY: 17438 AN XY: 73502

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.254

Alfa AF: 0.268 Hom.: 2646

Bravo AF: 0.236

Asia WGS AF: 0.0650 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.0
Dann	Benign	0.69

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: rs3120701; hg19: chr1-246706139;