14-105210578-A-G

Variant names:

• chr14-105210578-A-G
• rs150636332
• NM_001519.4:c.2007T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_001519.4(BRF1):​c.2007T>C​(p.Cys669Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,611,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: BRF1 NM_001519.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.10
• Publications: 0 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: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• 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 (BayesDel_noAF=-0.51).
• BP6: Variant 14-105210578-A-G is Benign according to our data. Variant chr14-105210578-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 735819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000204 (31/152028) while in subpopulation AMR AF = 0.0019 (29/15270). AF 95% confidence interval is 0.00136. There are 1 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001519.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRF1	NM_001519.4	MANE Select	c.2007T>C	p.Cys669Cys	synonymous	Exon 18 of 18	NP_001510.2
	BRF1	NM_001440449.1		c.2004T>C	p.Cys668Cys	synonymous	Exon 18 of 18	NP_001427378.1
	BRF1	NM_001242788.2		c.1926T>C	p.Cys642Cys	synonymous	Exon 17 of 17	NP_001229717.1	Q92994-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRF1	ENST00000547530.7	TSL:1 MANE Select	c.2007T>C	p.Cys669Cys	synonymous	Exon 18 of 18	ENSP00000448387.2	Q92994-1
	BRF1	ENST00000379937.6	TSL:1	c.1926T>C	p.Cys642Cys	synonymous	Exon 17 of 17	ENSP00000369269.2	Q92994-5
	BRF1	ENST00000392557.8	TSL:1	c.1395T>C	p.Cys465Cys	synonymous	Exon 14 of 14	ENSP00000376340.4	Q92994-3

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152028 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000976 AC: 24 AN: 245904 AF XY: 0.0000823

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1459136 Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19 AN XY: 725840

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000492 AC: 22 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111856

Other (OTH) AF: 0.0000829 AC: 5 AN: 60336

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152028 Hom.: 1 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41362

American (AMR) AF: 0.00190 AC: 29 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000257

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.64
PhyloP100		3.1

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

Other links and lift over

dbSNP: rs150636332; hg19: chr14-105676915;