rs1008628

Positions:

• chr14-105256389-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000548421.2(BRF1):​c.600A>G​(p.Pro200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,602,464 control chromosomes in the GnomAD database, including 61,258 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 0.26 (5235 hom., cov: 32)
  • Exomes 𝑓: 0.28 (56023 hom.)
• Consequence: BRF1 ENST00000548421.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

Genes affected

BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) 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
BRF1	NM_001519.4	c.471+129A>G		intron_variant		ENST00000547530.7	NP_001510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRF1	ENST00000547530.7	c.471+129A>G		intron_variant		1	NM_001519.4	ENSP00000448387	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38950 AN: 151866 Hom.: 5228 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.249

GnomAD3 exomes AF: 0.262 AC: 60563 AN: 230790 Hom.: 8124 AF XY: 0.269 AC XY: 33645 AN XY: 125208

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.136

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.276 AC: 399954 AN: 1450480 Hom.: 56023 Cov.: 36 AF XY: 0.277 AC XY: 199324 AN XY: 720798

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.257 AC: 38985 AN: 151984 Hom.: 5235 Cov.: 32 AF XY: 0.256 AC XY: 19040 AN XY: 74270

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.246

Alfa AF: 0.267 Hom.: 1517

Bravo AF: 0.248

Asia WGS AF: 0.199 AC: 695 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.52
DANN	Benign	0.45

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: rs1008628; hg19: chr14-105722726; COSMIC: COSV59271064;