18-26265280-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005640.3(TAF4B):c.454G>A(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,964 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A152V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0096 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (19 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.201

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024737418).
• BP6: Variant 18-26265280-G-A is Benign according to our data. Variant chr18-26265280-G-A is described in ClinVar as [Benign]. Clinvar id is 714746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0096 (1462/152262) while in subpopulation AFR AF= 0.0326 (1356/41534). 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 GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF4B	NM_005640.3	c.454G>A	p.Ala152Thr	missense_variant	2/15	ENST00000269142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4B	ENST00000269142.10	c.454G>A	p.Ala152Thr	missense_variant	2/15	1	NM_005640.3	P4
TAF4B	ENST00000578121.5	c.454G>A	p.Ala152Thr	missense_variant	2/15	2		A2
TAF4B	ENST00000418698.3	c.454G>A	p.Ala152Thr	missense_variant, NMD_transcript_variant	2/16	5

Frequencies

GnomAD3 genomes AF: 0.00960 AC: 1461 AN: 152144 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0327

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: 0.00956

GnomAD3 exomes AF: 0.00272 AC: 679 AN: 249372 Hom.: 9 AF XY: 0.00194 AC XY: 263 AN XY: 135314

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00311

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00114 AC: 1662 AN: 1461702 Hom.: 19 Cov.: 31 AF XY: 0.000983 AC XY: 715 AN XY: 727158

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome AF: 0.00960 AC: 1462 AN: 152262 Hom.: 12 Cov.: 32 AF XY: 0.00915 AC XY: 681 AN XY: 74454

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.00458

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: 0.00946

Alfa AF: 0.00171 Hom.: 6

Bravo AF: 0.0113

ESP6500AA AF: 0.0277 AC: 107

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.00319 AC: 386

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.20
Dann	Benign	0.81
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.60	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.95	N;.
REVEL	Benign	0.092
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.049
MVP		0.27
MPC		0.036
ClinPred		0.0035	T
GERP RS		-10
Varity_R		0.029
gMVP		0.17

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: rs77520691; hg19: chr18-23845244;