rs2492937

Positions:

• chr6-42086608-G-A

Variant summary

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

The NM_001410907.1(TAF8):​c.921-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,063,322 control chromosomes in the GnomAD database, including 26,731 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 0.28 (8968 hom., cov: 32)
  • Exomes 𝑓: 0.18 (17763 hom.)
• Consequence: TAF8 NM_001410907.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

Genes affected

TAF8 (HGNC:17300): (TATA-box binding protein associated factor 8) This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF8	NM_001410907.1	c.921-111G>A		intron_variant			NP_001397836.1
TAF8	XM_047418174.1	c.*26-111G>A		intron_variant			XP_047274130.1
TAF8	XM_047418177.1	c.*26-111G>A		intron_variant			XP_047274133.1
TAF8	XM_047418178.1	c.630-111G>A		intron_variant			XP_047274134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF8	ENST00000456846.6	c.921-111G>A		intron_variant		1		ENSP00000411900.2
TAF8	ENST00000372982.8	c.*26-111G>A		intron_variant		2		ENSP00000362073.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42732 AN: 151938 Hom.: 8940 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.181 AC: 165286 AN: 911266 Hom.: 17763 AF XY: 0.178 AC XY: 83626 AN XY: 468924

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.282 AC: 42808 AN: 152056 Hom.: 8968 Cov.: 32 AF XY: 0.274 AC XY: 20355 AN XY: 74346

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0927

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.249

Alfa AF: 0.190 Hom.: 3262

Bravo AF: 0.299

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2492937; hg19: chr6-42054346;