18-26227063-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005640.3(TAF4B):c.130G>C(p.Ala44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,595,256 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (97 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.798

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=0.001581341).
• BP6: Variant 18-26227063-G-C is Benign according to our data. Variant chr18-26227063-G-C is described in ClinVar as [Benign]. Clinvar id is 778769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF4B	NM_005640.3	c.130G>C	p.Ala44Pro	missense_variant	1/15	ENST00000269142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4B	ENST00000269142.10	c.130G>C	p.Ala44Pro	missense_variant	1/15	1	NM_005640.3	P4
TAF4B	ENST00000578121.5	c.130G>C	p.Ala44Pro	missense_variant	1/15	2		A2
TAF4B	ENST00000418698.3	c.130G>C	p.Ala44Pro	missense_variant, NMD_transcript_variant	1/16	5

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2708 AN: 152094 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00433 AC: 931 AN: 215246 Hom.: 34 AF XY: 0.00310 AC XY: 371 AN XY: 119626

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000342

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000136

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00194 AC: 2796 AN: 1443046 Hom.: 97 Cov.: 31 AF XY: 0.00167 AC XY: 1196 AN XY: 718122

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome AF: 0.0178 AC: 2716 AN: 152210 Hom.: 67 Cov.: 32 AF XY: 0.0172 AC XY: 1282 AN XY: 74418

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00741 Hom.: 7

Bravo AF: 0.0196

ESP6500AA AF: 0.0520 AC: 196

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00507 AC: 609

Asia WGS AF: 0.00289 AC: 10 AN: 3478

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

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	20
Dann	Benign	0.93
DEOGEN2	Benign	0.047	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.44	N;.
REVEL	Benign	0.013
Sift	Benign	0.20	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.0060	B;.
Vest4		0.10
MVP		0.12
MPC		1.0
ClinPred		0.021	T
GERP RS		1.5
Varity_R		0.078
gMVP		0.42

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: rs78262333; hg19: chr18-23807027;