rs8083533

Positions:

• chr18-26350760-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005640.3(TAF4B):​c.2317-6930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,008 control chromosomes in the GnomAD database, including 7,024 homozygotes. 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 0.29 (7024 hom., cov: 32)
• Consequence: TAF4B NM_005640.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.2317-6930G>A		intron_variant		ENST00000269142.10	NP_005631.1
TAF4B	NM_001293725.2	c.2332-6930G>A		intron_variant			NP_001280654.1
TAF4B	XM_024451239.2	c.2317-6930G>A		intron_variant			XP_024307007.1
TAF4B	NR_121653.2	n.2926-6930G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.2317-6930G>A		intron_variant		1	NM_005640.3	ENSP00000269142	P4
TAF4B	ENST00000578121.5	c.2332-6930G>A		intron_variant		2		ENSP00000462980	A2
TAF4B	ENST00000418698.3	c.*580-6930G>A		intron_variant, NMD_transcript_variant		5		ENSP00000389365

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44625 AN: 151890 Hom.: 7009 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44680 AN: 152008 Hom.: 7024 Cov.: 32 AF XY: 0.286 AC XY: 21292 AN XY: 74318

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0703

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.264

Alfa AF: 0.288 Hom.: 5965

Bravo AF: 0.287

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.46

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: rs8083533; hg19: chr18-23930724;