rs3000073

Positions:

• chr14-105263455-G-A

Variant summary

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

The ENST00000547530.7(BRF1):​c.440-6906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,788 control chromosomes in the GnomAD database, including 6,253 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 (6253 hom., cov: 30)
• Consequence: BRF1 ENST00000547530.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.98

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRF1	NM_001519.4	c.440-6906C>T		intron_variant		ENST00000547530.7	NP_001510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRF1	ENST00000547530.7	c.440-6906C>T		intron_variant		1	NM_001519.4	ENSP00000448387	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42782 AN: 151670 Hom.: 6241 Cov.: 30

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.282 AC: 42829 AN: 151788 Hom.: 6253 Cov.: 30 AF XY: 0.282 AC XY: 20922 AN XY: 74150

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.265

Alfa AF: 0.284 Hom.: 5411

Bravo AF: 0.273

Asia WGS AF: 0.205 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.82
DANN	Benign	0.44

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: rs3000073; hg19: chr14-105729792; COSMIC: COSV59269744;