18-26265281-C-T

Variant names:

• chr18-26265281-C-T
• rs75981934
• NM_005640.3:c.455C>T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

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=0.0028557777).
• 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 rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.455C>T	p.Ala152Val	missense_variant	Exon 2 of 15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.455C>T	p.Ala152Val	missense_variant	Exon 2 of 15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.455C>T	p.Ala152Val	missense_variant	Exon 2 of 15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.455C>T		non_coding_transcript_exon_variant	Exon 2 of 16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes AF: 0.00961 AC: 1461 AN: 152074 Hom.: 12 Cov.: 32

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.: 9 AF XY: 0.00196 AC XY: 265 AN XY: 135286

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.: 19 Cov.: 31 AF XY: 0.00101 AC XY: 731 AN XY: 727102

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.: 12 Cov.: 32 AF XY: 0.00915 AC XY: 681 AN XY: 74406

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.: 4

Bravo AF: 0.0113

ESP6500AA AF: 0.0277 AC: 107

ESP6500EA AF: 0.000362 AC: 3

ExAC AF: 0.00322 AC: 389

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.70	T
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	N
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0029	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;.
PrimateAI	Benign	0.25	T
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	T
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

Other links and lift over

dbSNP: rs75981934; hg19: chr18-23845245;