8-37847111-CGC-GGT

Variant names:

• chr8-37847111-CGC-GGT
• NM_018310.4:c.277_279delGCGinsACC
• BRF2 p.Ala93Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018310.4(BRF2):​c.277_279delGCGinsACC​(p.Ala93Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRF2 NM_018310.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.96
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018310.4. 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
	BRF2	NM_018310.4	MANE Select	c.277_279delGCGinsACC	p.Ala93Thr	missense	N/A	NP_060780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRF2	ENST00000220659.11	TSL:1 MANE Select	c.277_279delGCGinsACC	p.Ala93Thr	missense	N/A	ENSP00000220659.6	Q9HAW0-1
	BRF2	ENST00000714160.1		c.277_279delGCGinsACC	p.Ala93Thr	missense	N/A	ENSP00000519449.1	A0AAQ5BHI0
	BRF2	ENST00000520601.5	TSL:3	c.277_279delGCGinsACC	p.Ala93Thr	missense	N/A	ENSP00000430107.1	E5RGX1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-37704629;