rs2735816

Positions:

• chr14-105255266-G-C

Variant summary

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

The NM_001519.4(BRF1):​c.471+1252C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,250 control chromosomes in the GnomAD database, including 5,280 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 (5280 hom., cov: 33)
• Consequence: BRF1 NM_001519.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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=-1.0).
• 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+1252C>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+1252C>G		intron_variant		1	NM_001519.4	ENSP00000448387.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39125 AN: 152130 Hom.: 5273 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.257 AC: 39160 AN: 152250 Hom.: 5280 Cov.: 33 AF XY: 0.257 AC XY: 19134 AN XY: 74432

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.247

Alfa AF: 0.259 Hom.: 651

Bravo AF: 0.248

Asia WGS AF: 0.199 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.46

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: rs2735816; hg19: chr14-105721603;