1-28624350-C-T

Variant names:

• chr1-28624350-C-T
• rs4316338
• NM_005644.4:c.-84-2185G>A

Variant summary

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

The NM_005644.4(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 NM_005644.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005644.4. 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
	TAF12	NM_005644.4	MANE Select	c.-84-2185G>A		intron	N/A	NP_005635.1	Q16514-1
	TAF12	NM_001410769.1		c.-13-320G>A		intron	N/A	NP_001397698.1	A0A804HLG9
	TAF12	NM_001135218.2		c.-84-2185G>A		intron	N/A	NP_001128690.1	Q16514-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF12	ENST00000373824.9	TSL:1 MANE Select	c.-84-2185G>A		intron	N/A	ENSP00000362930.4	Q16514-1
	TAF12	ENST00000263974.4	TSL:1	c.-84-2185G>A		intron	N/A	ENSP00000263974.4	Q16514-1
	TAF12	ENST00000688108.1		c.-84-2185G>A		intron	N/A	ENSP00000510282.1	A0A8I5KTB6

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

African (AFR) AF: 0.126 AC: 5240 AN: 41512

American (AMR) AF: 0.223 AC: 3388 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3470

East Asian (EAS) AF: 0.0845 AC: 438 AN: 5186

South Asian (SAS) AF: 0.178 AC: 859 AN: 4820

European-Finnish (FIN) AF: 0.279 AC: 2938 AN: 10548

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18906 AN: 67970

Other (OTH) AF: 0.252 AC: 530 AN: 2100

Alfa AF: 0.243 Hom.: 2847

Bravo AF: 0.217

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.50
PhyloP100		0.53
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: rs4316338; hg19: chr1-28950862;