8-37844737-A-C

Variant names:

• chr8-37844737-A-C
• rs150785651
• NM_018310.4:c.1013T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018310.4(BRF2):​c.1013T>G​(p.Val338Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: BRF2 NM_018310.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.623
• 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]

ADGRA2 (HGNC:17849): (adhesion G protein-coupled receptor A2) Predicted to enable G protein-coupled receptor activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069716275).

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.1013T>G	p.Val338Gly	missense	Exon 4 of 4	NP_060780.2
	ADGRA2	NM_032777.10	MANE Select	c.*2382A>C		3_prime_UTR	Exon 19 of 19	NP_116166.9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRF2	ENST00000220659.11	TSL:1 MANE Select	c.1013T>G	p.Val338Gly	missense	Exon 4 of 4	ENSP00000220659.6	Q9HAW0-1
	ADGRA2	ENST00000412232.3	TSL:1 MANE Select	c.*2382A>C		3_prime_UTR	Exon 19 of 19	ENSP00000406367.2	Q96PE1-1
	ADGRA2	ENST00000315215.11	TSL:1	c.*2382A>C		3_prime_UTR	Exon 16 of 16	ENSP00000323508.7	Q96PE1-2

Frequencies

GnomAD3 genomes AF: 0.000495 AC: 75 AN: 151640 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251192 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1461780 Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32 AN XY: 727184

African (AFR) AF: 0.00203 AC: 68 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.000494 AC: 75 AN: 151760 Hom.: 0 Cov.: 32 AF XY: 0.000418 AC XY: 31 AN XY: 74134

African (AFR) AF: 0.00172 AC: 71 AN: 41334

American (AMR) AF: 0.000197 AC: 3 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000488 Hom.: 1

Bravo AF: 0.000563

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.8
DANN	Benign	0.68
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.62
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.015
Sift	Benign	0.37	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.36
MPC		0.19
ClinPred		0.014	T
GERP RS		-3.6
Varity_R		0.060
gMVP		0.27
Mutation Taster		=98/2	polymorphism

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: rs150785651; hg19: chr8-37702255;