rs8083533

Variant names:

• chr18-26350760-G-A
• rs8083533
• NM_005640.3:c.2317-6930G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TAF4B Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 13

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005640.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	NM_005640.3	MANE Select	c.2317-6930G>A		intron	N/A	NP_005631.1	Q92750-1
	TAF4B	NM_001293725.2		c.2332-6930G>A		intron	N/A	NP_001280654.1	J3KTH2
	TAF4B	NR_121653.2		n.2926-6930G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	ENST00000269142.10	TSL:1 MANE Select	c.2317-6930G>A		intron	N/A	ENSP00000269142.6	Q92750-1
	TAF4B	ENST00000935352.1		c.2416-6930G>A		intron	N/A	ENSP00000605411.1
	TAF4B	ENST00000935354.1		c.2359-6930G>A		intron	N/A	ENSP00000605413.1

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

African (AFR) AF: 0.359 AC: 14878 AN: 41438

American (AMR) AF: 0.203 AC: 3109 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.0703 AC: 364 AN: 5180

South Asian (SAS) AF: 0.125 AC: 604 AN: 4824

European-Finnish (FIN) AF: 0.328 AC: 3466 AN: 10560

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20496 AN: 67940

Other (OTH) AF: 0.264 AC: 556 AN: 2110

Alfa AF: 0.292 Hom.: 11553

Bravo AF: 0.287

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.46
PhyloP100		0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8083533; hg19: chr18-23930724;