chr14-55430820-A-G

Variant names:

• chr14-55430820-A-G
• rs4470077
• NM_199047.3:c.693-1846T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199047.3(TBPL2):​c.693-1846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,166 control chromosomes in the GnomAD database, including 7,731 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 0.28 (7731 hom., cov: 32)
• Consequence: TBPL2 NM_199047.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 5 publications found

Genes affected

TBPL2 (HGNC:19841): (TATA-box binding protein like 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Predicted to be involved in DNA-templated transcription, initiation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FBXO34 (HGNC:20201): (F-box protein 34) Members of the F-box protein family, such as FBXO34, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199047.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBPL2	NM_199047.3	MANE Select	c.693-1846T>C		intron	N/A	NP_950248.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBPL2	ENST00000247219.6	TSL:1 MANE Select	c.693-1846T>C		intron	N/A	ENSP00000247219.6

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42506 AN: 152048 Hom.: 7709 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.280 AC: 42578 AN: 152166 Hom.: 7731 Cov.: 32 AF XY: 0.275 AC XY: 20422 AN XY: 74394

African (AFR) AF: 0.525 AC: 21780 AN: 41484

American (AMR) AF: 0.187 AC: 2864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0941 AC: 488 AN: 5188

South Asian (SAS) AF: 0.186 AC: 897 AN: 4826

European-Finnish (FIN) AF: 0.191 AC: 2029 AN: 10596

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12988 AN: 68004

Other (OTH) AF: 0.252 AC: 532 AN: 2112

Alfa AF: 0.233 Hom.: 1086

Bravo AF: 0.291

Asia WGS AF: 0.184 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		-0.39
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: rs4470077; hg19: chr14-55897538;