rs2735816

Variant names:

• chr14-105255266-G-C
• rs2735816
• NM_001519.4:c.471+1252C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

BRF1 Gene-Disease associations (from GenCC):

• cerebellar-facial-dental syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia, Ambry Genetics
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BRF1	NM_001519.4	c.471+1252C>G		intron_variant	Intron 4 of 17	ENST00000547530.7	NP_001510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRF1	ENST00000547530.7	c.471+1252C>G		intron_variant	Intron 4 of 17	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

African (AFR) AF: 0.235 AC: 9765 AN: 41554

American (AMR) AF: 0.195 AC: 2990 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3472

East Asian (EAS) AF: 0.144 AC: 747 AN: 5182

South Asian (SAS) AF: 0.288 AC: 1390 AN: 4832

European-Finnish (FIN) AF: 0.344 AC: 3645 AN: 10588

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18953 AN: 68006

Other (OTH) AF: 0.247 AC: 523 AN: 2114

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2735816; hg19: chr14-105721603;