chr18-26312708-G-A

Variant names:

• chr18-26312708-G-A
• rs1791780
• NM_005640.3:c.1833-2521G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001293725.2(TAF4B):​c.1848-2521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,946 control chromosomes in the GnomAD database, including 14,270 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 0.40 (14270 hom., cov: 31)
• Consequence: TAF4B NM_001293725.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293725.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	NM_005640.3	MANE Select	c.1833-2521G>A		intron	N/A	NP_005631.1
	TAF4B	NM_001293725.2		c.1848-2521G>A		intron	N/A	NP_001280654.1
	TAF4B	NR_121653.2		n.2442-2521G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF4B	ENST00000269142.10	TSL:1 MANE Select	c.1833-2521G>A		intron	N/A	ENSP00000269142.6
	TAF4B	ENST00000935352.1		c.1833-2521G>A		intron	N/A	ENSP00000605411.1
	TAF4B	ENST00000935354.1		c.1875-2521G>A		intron	N/A	ENSP00000605413.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60053 AN: 151828 Hom.: 14256 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.395 AC: 60071 AN: 151946 Hom.: 14270 Cov.: 31 AF XY: 0.405 AC XY: 30044 AN XY: 74250

African (AFR) AF: 0.138 AC: 5727 AN: 41474

American (AMR) AF: 0.479 AC: 7317 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3468

East Asian (EAS) AF: 0.808 AC: 4156 AN: 5146

South Asian (SAS) AF: 0.634 AC: 3050 AN: 4810

European-Finnish (FIN) AF: 0.469 AC: 4938 AN: 10530

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31440 AN: 67940

Other (OTH) AF: 0.431 AC: 911 AN: 2112

Alfa AF: 0.438 Hom.: 25556

Bravo AF: 0.384

Asia WGS AF: 0.625 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.56
PhyloP100		0.11
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: rs1791780; hg19: chr18-23892672;