Variant 18-26265281-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005640.3(TAF4B):c.455C>T(p.Ala152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,804 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 19 hom. )

Consequence

TAF4B
NM_005640.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

TAF4B (HGNC:11538): (TATA-box binding protein associated factor 4b) TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

TAF4B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028557777).

BP6

Variant 18-26265281-C-T is Benign according to our data. Variant chr18-26265281-C-T is described in ClinVar as [Benign]. Clinvar id is 714747.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00961 (1462/152192) while in subpopulation AFR AF= 0.0327 (1356/41486). AF 95% confidence interval is 0.0312. There are 12 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF4B	NM_005640.3 linkuse as main transcript	c.455C>T	p.Ala152Val	missense_variant	2/15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10 linkuse as main transcript	c.455C>T	p.Ala152Val	missense_variant	2/15	1	NM_005640.3	ENSP00000269142	P4	Q92750-1
TAF4B	ENST00000578121.5 linkuse as main transcript	c.455C>T	p.Ala152Val	missense_variant	2/15	2		ENSP00000462980	A2
TAF4B	ENST00000418698.3 linkuse as main transcript	c.455C>T	p.Ala152Val	missense_variant, NMD_transcript_variant	2/16	5		ENSP00000389365		Q92750-2

Frequencies

GnomAD3 genomes

AF:

0.00961

AC:

1461

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00275

AC:

685

AN:

249312

Hom.:

AF XY:

0.00196

AC XY:

265

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000274

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00116

AC:

1694

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

731

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.00336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.00961

AC:

1462

AN:

152192

Hom.:

Cov.:

AF XY:

0.00915

AC XY:

681

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.0113

ESP6500AA

AF:

0.0277

AC:

107

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.00322

AC:

389

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.5

DANN

Benign

0.80

DEOGEN2

Benign

0.066

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.79

N;.

REVEL

Benign

0.012

Sift

Benign

0.12

T;.

Sift4G

Benign

0.15

T;T

Polyphen

0.0020

B;.

Vest4

0.054

MVP

0.19

MPC

0.036

ClinPred

0.0026

GERP RS

0.33

Varity_R

0.036

gMVP

0.22

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

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