chr1-246542837-C-T

Variant names:

• chr1-246542837-C-T
• rs3120701
• NM_022366.3:c.1020-1635G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022366.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFB2M	NM_022366.3	MANE Select	c.1020-1635G>A		intron	N/A	NP_071761.1	Q9H5Q4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFB2M	ENST00000366514.5	TSL:1 MANE Select	c.1020-1635G>A		intron	N/A	ENSP00000355471.4	Q9H5Q4
	TFB2M	ENST00000873624.1		c.957-1635G>A		intron	N/A	ENSP00000543683.1
	TFB2M	ENST00000873625.1		c.930-1635G>A		intron	N/A	ENSP00000543684.1

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

African (AFR) AF: 0.195 AC: 7978 AN: 40934

American (AMR) AF: 0.234 AC: 3541 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5154

South Asian (SAS) AF: 0.125 AC: 598 AN: 4766

European-Finnish (FIN) AF: 0.266 AC: 2706 AN: 10158

Middle Eastern (MID) AF: 0.438 AC: 126 AN: 288

European-Non Finnish (NFE) AF: 0.288 AC: 19541 AN: 67900

Other (OTH) AF: 0.254 AC: 529 AN: 2086

Alfa AF: 0.270 Hom.: 2955

Bravo AF: 0.236

Asia WGS AF: 0.0650 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3120701; hg19: chr1-246706139;