Variant chr14-105209632-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The ENST00000551787.5(BRF1):c.430G>A(p.Gly144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 693,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

BRF1
ENST00000551787.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0280

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046993107).

BP6

Variant 14-105209632-C-T is Benign according to our data. Variant chr14-105209632-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1711377.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000361 (55/152348) while in subpopulation NFE AF= 0.000676 (46/68020). AF 95% confidence interval is 0.000521. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRF1	NM_001519.4 linkuse as main transcript	c.*919G>A		3_prime_UTR_variant	18/18	ENST00000547530.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRF1	ENST00000547530.7 linkuse as main transcript	c.*919G>A		3_prime_UTR_variant	18/18	1	NM_001519.4	P1	Q92994-1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

129748

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

70564

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000961

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000776

Gnomad NFE exome

AF:

0.000393

Gnomad OTH exome

AF:

0.000761

GnomAD4 exome

AF:

0.000508

AC:

275

AN:

541568

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

153

AN XY:

292390

show subpopulations

Gnomad4 AFR exome

AF:

0.0000641

Gnomad4 AMR exome

AF:

0.000207

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000570

Gnomad4 NFE exome

AF:

0.000758

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.000361

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

BRF1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.2

DANN

Benign

0.47

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.30

M_CAP

Benign

0.0019

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PROVEAN

Benign

-0.42

REVEL

Benign

0.049

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.013

Vest4

0.24

MutPred

0.19

Gain of MoRF binding (P = 0.0109);

MVP

0.043

ClinPred

0.015

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over