Genetic Variant BRF1:p.Trp205* (chr14-105256375-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242790.2(BRF1):c.614G>A(p.Trp205*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,510 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BRF1
NM_001242790.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

0 publications found

Variant links:

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: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
colorectal adenoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRF1	NM_001519.4	MANE Select	c.471+143G>A		intron	N/A	NP_001510.2
BRF1	NM_001242790.2		c.614G>A	p.Trp205*	stop_gained	Exon 4 of 4	NP_001229719.1	Q92994-6
BRF1	NM_001440449.1		c.471+143G>A		intron	N/A	NP_001427378.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRF1	ENST00000548421.2	TSL:1	c.614G>A	p.Trp205*	stop_gained	Exon 4 of 4	ENSP00000446707.1	Q92994-6
BRF1	ENST00000547530.7	TSL:1 MANE Select	c.471+143G>A		intron	N/A	ENSP00000448387.2	Q92994-1
BRF1	ENST00000379937.6	TSL:1	c.390+143G>A		intron	N/A	ENSP00000369269.2	Q92994-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000954

AC:

AN:

209552

AF XY:

0.00000883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1436510

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32740

American (AMR)

AF:

0.00

AC:

AN:

39836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25694

East Asian (EAS)

AF:

0.0000527

AC:

AN:

37982

South Asian (SAS)

AF:

0.00

AC:

AN:

83182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100624

Other (OTH)

AF:

0.00

AC:

AN:

59596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.46

(source)

DANN

Benign

0.54

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0018

PhyloP100

-1.3

Vest4

0.023

GERP RS

-2.4

Mutation Taster

=193/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over