chr14-105256389-T-C

Variant names:

• chr14-105256389-T-C
• rs1008628
• ENST00000548421.2:c.600A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000548421.2(BRF1):​c.600A>G​(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,602,464 control chromosomes in the GnomAD database, including 61,258 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 0.26 (5235 hom., cov: 32)
  • Exomes 𝑓: 0.28 (56023 hom.)
• Consequence: BRF1 ENST00000548421.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 22 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.116).
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRF1	NM_001519.4	c.471+129A>G		intron_variant	Intron 4 of 17	ENST00000547530.7	NP_001510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRF1	ENST00000547530.7	c.471+129A>G		intron_variant	Intron 4 of 17	1	NM_001519.4	ENSP00000448387.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38950 AN: 151866 Hom.: 5228 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.262 AC: 60563 AN: 230790 AF XY: 0.269

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.276 AC: 399954 AN: 1450480 Hom.: 56023 Cov.: 36 AF XY: 0.277 AC XY: 199324 AN XY: 720798

African (AFR) AF: 0.237 AC: 7860 AN: 33202

American (AMR) AF: 0.207 AC: 8802 AN: 42430

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6180 AN: 25942

East Asian (EAS) AF: 0.167 AC: 6529 AN: 39048

South Asian (SAS) AF: 0.286 AC: 24286 AN: 84934

European-Finnish (FIN) AF: 0.335 AC: 17458 AN: 52134

Middle Eastern (MID) AF: 0.296 AC: 1704 AN: 5756

European-Non Finnish (NFE) AF: 0.281 AC: 311125 AN: 1107022

Other (OTH) AF: 0.267 AC: 16010 AN: 60012

GnomAD4 genome AF: 0.257 AC: 38985 AN: 151984 Hom.: 5235 Cov.: 32 AF XY: 0.256 AC XY: 19040 AN XY: 74270

African (AFR) AF: 0.235 AC: 9717 AN: 41428

American (AMR) AF: 0.195 AC: 2977 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.143 AC: 739 AN: 5158

South Asian (SAS) AF: 0.287 AC: 1380 AN: 4810

European-Finnish (FIN) AF: 0.343 AC: 3623 AN: 10556

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18893 AN: 67970

Other (OTH) AF: 0.246 AC: 518 AN: 2104

Alfa AF: 0.259 Hom.: 2570

Bravo AF: 0.248

Asia WGS AF: 0.199 AC: 695 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.52
DANN	Benign	0.45
PhyloP100		-2.2
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: rs1008628; hg19: chr14-105722726; COSMIC: COSV59271064;