rs4800250

Variant names:

• chr18-26230803-G-A
• rs4800250
• NM_005640.3:c.343+3527G>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.343+3527G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,980 control chromosomes in the GnomAD database, including 33,671 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 0.64 (33671 hom., cov: 30)
• Consequence: TAF4B NM_005640.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.343+3527G>A		intron_variant	Intron 1 of 14	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.343+3527G>A		intron_variant	Intron 1 of 14	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.343+3527G>A		intron_variant	Intron 1 of 14	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.343+3527G>A		intron_variant	Intron 1 of 15	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97803 AN: 151862 Hom.: 33615 Cov.: 30

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.644 AC: 97902 AN: 151980 Hom.: 33671 Cov.: 30 AF XY: 0.634 AC XY: 47090 AN XY: 74266

African (AFR) AF: 0.874 AC: 36254 AN: 41478

American (AMR) AF: 0.570 AC: 8705 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.192 AC: 993 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1662 AN: 4808

European-Finnish (FIN) AF: 0.576 AC: 6065 AN: 10530

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

European-Non Finnish (NFE) AF: 0.595 AC: 40414 AN: 67950

Other (OTH) AF: 0.609 AC: 1286 AN: 2110

Alfa AF: 0.605 Hom.: 58907

Bravo AF: 0.656

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		0.031
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: rs4800250; hg19: chr18-23810767;