14-105217208-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001519.4(BRF1):c.1772+336T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 440,476 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (13 hom.)
• Consequence: BRF1 NM_001519.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 14-105217208-A-C is Benign according to our data. Variant chr14-105217208-A-C is described in ClinVar as [Benign]. Clinvar id is 2644905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00626 (953/152350) while in subpopulation SAS AF= 0.0141 (68/4828). AF 95% confidence interval is 0.0114. There are 12 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRF1	NM_001519.4	c.1772+336T>G		intron_variant		ENST00000547530.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRF1	ENST00000547530.7	c.1772+336T>G		intron_variant		1	NM_001519.4	P1

Frequencies

GnomAD3 genomes AF: 0.00625 AC: 952 AN: 152232 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00861

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00759 AC: 2187 AN: 288126 Hom.: 13 Cov.: 0 AF XY: 0.00826 AC XY: 1230 AN XY: 148876

Gnomad4 AFR exome AF: 0.00106

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0155

Gnomad4 FIN exome AF: 0.00963

Gnomad4 NFE exome AF: 0.00797

Gnomad4 OTH exome AF: 0.00698

GnomAD4 genome AF: 0.00626 AC: 953 AN: 152350 Hom.: 12 Cov.: 33 AF XY: 0.00651 AC XY: 485 AN XY: 74504

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.00862

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00762 Hom.: 2

Bravo AF: 0.00483

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

BRF1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.40
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs587622880; hg19: chr14-105683545;