18-26227080-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_005640.3(TAF4B):c.147T>C(p.Pro49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,606,964 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (12 hom.)
• Consequence: TAF4B NM_005640.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.322

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 18-26227080-T-C is Benign according to our data. Variant chr18-26227080-T-C is described in ClinVar as [Benign]. Clinvar id is 786339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.322 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00663 (1010/152230) while in subpopulation AFR AF= 0.0233 (970/41546). AF 95% confidence interval is 0.0221. There are 12 homozygotes in gnomad4. There are 446 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.147T>C	p.Pro49=	synonymous_variant	1/15	ENST00000269142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4B	ENST00000269142.10	c.147T>C	p.Pro49=	synonymous_variant	1/15	1	NM_005640.3	P4
TAF4B	ENST00000578121.5	c.147T>C	p.Pro49=	synonymous_variant	1/15	2		A2
TAF4B	ENST00000418698.3	c.147T>C	p.Pro49=	synonymous_variant, NMD_transcript_variant	1/16	5

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1006 AN: 152114 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

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: 0.000147

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00162 AC: 378 AN: 233428 Hom.: 4 AF XY: 0.00113 AC XY: 145 AN XY: 128206

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.000845

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.000879

GnomAD4 exome AF: 0.000702 AC: 1021 AN: 1454734 Hom.: 12 Cov.: 31 AF XY: 0.000620 AC XY: 449 AN XY: 723922

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.000910

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000816

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000559

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00663 AC: 1010 AN: 152230 Hom.: 12 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74432

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00771

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	10
Dann	Benign	0.75

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: rs60311681; hg19: chr18-23807044;