18-26227080-T-G

Variant names:

• chr18-26227080-T-G
• rs60311681
• NM_005640.3:c.147T>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005640.3(TAF4B):​c.147T>G​(p.Pro49Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000996 in 1,606,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: TAF4B NM_005640.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.322 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.147T>G	p.Pro49Pro	synonymous_variant	Exon 1 of 15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.147T>G	p.Pro49Pro	synonymous_variant	Exon 1 of 15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.147T>G	p.Pro49Pro	synonymous_variant	Exon 1 of 15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.147T>G		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233428 Hom.: 0 AF XY: 0.00000780 AC XY: 1 AN XY: 128206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000961

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1454736 Hom.: 0 Cov.: 31 AF XY: 0.00000829 AC XY: 6 AN XY: 723924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000991

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74308

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.7
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;