rs3000073

Variant names:

• chr14-105263455-G-A
• rs3000073
• NM_001519.4:c.440-6906C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001519.4(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 NM_001519.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.98
• Publications: 25 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=-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 rank	MANE	Protein	UniProt
BRF1	NM_001519.4	c.440-6906C>T		intron_variant	Intron 3 of 17	ENST00000547530.7	NP_001510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRF1	ENST00000547530.7	c.440-6906C>T		intron_variant	Intron 3 of 17	1	NM_001519.4	ENSP00000448387.2

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

African (AFR) AF: 0.285 AC: 11805 AN: 41434

American (AMR) AF: 0.209 AC: 3182 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3466

East Asian (EAS) AF: 0.143 AC: 732 AN: 5128

South Asian (SAS) AF: 0.296 AC: 1422 AN: 4800

European-Finnish (FIN) AF: 0.374 AC: 3922 AN: 10490

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20038 AN: 67910

Other (OTH) AF: 0.265 AC: 558 AN: 2108

Alfa AF: 0.284 Hom.: 17989

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
PhyloP100		-5.0
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: rs3000073; hg19: chr14-105729792; COSMIC: COSV59269744;