Variant 14-55428815-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000247219.6(TBPL2):c.852G>A(p.Gln284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,613,860 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 25 hom. )

Consequence

TBPL2
ENST00000247219.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.860

Variant links:

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]

TBPL2 links:

FBXO34 (HGNC:):

FBXO34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 14-55428815-C-T is Benign according to our data. Variant chr14-55428815-C-T is described in ClinVar as [Benign]. Clinvar id is 711948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.86 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00781 (1189/152208) while in subpopulation AFR AF= 0.0221 (919/41532). AF 95% confidence interval is 0.0209. There are 10 homozygotes in gnomad4. There are 580 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBPL2	NM_199047.3 linkuse as main transcript	c.852G>A	p.Gln284=	synonymous_variant	5/7	ENST00000247219.6	NP_950248.2
FBXO34	XR_007064022.1 linkuse as main transcript	n.2982+4731C>T		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064023.1 linkuse as main transcript	n.2941-14012C>T		intron_variant, non_coding_transcript_variant
FBXO34	XR_007064024.1 linkuse as main transcript	n.2982+4731C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBPL2	ENST00000247219.6 linkuse as main transcript	c.852G>A	p.Gln284=	synonymous_variant	5/7	1	NM_199047.3	ENSP00000247219	P1

Frequencies

GnomAD3 genomes

AF:

0.00782

AC:

1190

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00386

AC:

969

AN:

251230

Hom.:

AF XY:

0.00362

AC XY:

491

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00331

AC:

4839

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

2427

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00597

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00781

AC:

1189

AN:

152208

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

580

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.00863

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over