rs16867195

Positions:

• chr2-9849313-A-G
• chr2-9849313-A-T

Variant summary

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

The NM_005680.3(TAF1B):​c.118-60A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,297,138 control chromosomes in the GnomAD database, including 56,937 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 0.24 (5002 hom., cov: 32)
  • Exomes 𝑓: 0.30 (51935 hom.)
• Consequence: TAF1B NM_005680.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

Genes affected

TAF1B (HGNC:11533): (TATA-box binding protein associated factor, RNA polymerase I subunit B) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes one of the SL1-specific TAFs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF1B	NM_005680.3	c.118-60A>G		intron_variant		ENST00000263663.10	NP_005671.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF1B	ENST00000263663.10	c.118-60A>G		intron_variant		1	NM_005680.3	ENSP00000263663	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36759 AN: 151940 Hom.: 5005 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.297 AC: 339767 AN: 1145080 Hom.: 51935 AF XY: 0.295 AC XY: 169226 AN XY: 573798

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.242 AC: 36748 AN: 152058 Hom.: 5002 Cov.: 32 AF XY: 0.244 AC XY: 18097 AN XY: 74302

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.246

Alfa AF: 0.280 Hom.: 7859

Bravo AF: 0.229

Asia WGS AF: 0.254 AC: 886 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.49

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: rs16867195; hg19: chr2-9989442; COSMIC: COSV55153897; COSMIC: COSV55153897;