rs4316338

Positions:

• chr1-28624350-C-T

Variant summary

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

The ENST00000373824.9(TAF12):​c.-84-2185G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,038 control chromosomes in the GnomAD database, including 4,129 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 0.22 (4129 hom., cov: 32)
• Consequence: TAF12 ENST00000373824.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

Genes affected

TAF12 (HGNC:11545): (TATA-box binding protein associated factor 12) Control of transcription by RNA polymerase II involves the basal transcription machinery which is a collection of proteins. These proteins with RNA polymerase II, assemble into complexes which are modulated by transactivator proteins that bind to cis-regulatory elements located adjacent to the transcription start site. Some modulators interact directly with the basal complex, whereas others may act as bridging proteins linking transactivators to the basal transcription factors. Some of these associated factors are weakly attached while others are tightly associated with TBP in the TFIID complex. Among the latter are the TAF proteins. Different TAFs are predicted to mediate the function of distinct transcriptional activators for a variety of gene promoters and RNA polymerases. TAF12 interacts directly with TBP as well as with TAF2I. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF12	NM_005644.4	c.-84-2185G>A		intron_variant		ENST00000373824.9	NP_005635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF12	ENST00000373824.9	c.-84-2185G>A		intron_variant		1	NM_005644.4	ENSP00000362930	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33546 AN: 151920 Hom.: 4128 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0850

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.221 AC: 33572 AN: 152038 Hom.: 4129 Cov.: 32 AF XY: 0.219 AC XY: 16283 AN XY: 74298

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.252

Alfa AF: 0.247 Hom.: 1454

Bravo AF: 0.217

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.50

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: rs4316338; hg19: chr1-28950862;