Variant rs142395337 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018310.4(BRF2):c.277G>A(p.Ala93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,614,218 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

BRF2
NM_018310.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 3.21

Variant links:

Genes affected

BRF2 (HGNC:17298): (BRF2 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the multiple subunits of the RNA polymerase III transcription factor complex required for transcription of genes with promoter elements upstream of the initiation site. The product of this gene, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with the TATA-binding protein. [provided by RefSeq, Jul 2008]

BRF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRF2	NM_018310.4 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/4	ENST00000220659.11	NP_060780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRF2	ENST00000220659.11 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/4	1	NM_018310.4	ENSP00000220659	P1	Q9HAW0-1
BRF2	ENST00000520601.5 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	3/5	3		ENSP00000430107
BRF2	ENST00000521170.5 linkuse as main transcript	c.*97G>A		3_prime_UTR_variant	4/4	4		ENSP00000430193
BRF2	ENST00000522539.1 linkuse as main transcript	c.*126G>A		3_prime_UTR_variant, NMD_transcript_variant	4/4	4		ENSP00000429554

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251456

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000764

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Malignant tumor of prostate

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

0.0016

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;.

Vest4

0.66

MVP

0.78

MPC

0.62

ClinPred

0.52

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.75

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