NM_139199.2:c.3148G>C

Variant names:

• chr5-138149770-C-G
• NM_139199.2:c.3148G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139199.2(BRD8):​c.3148G>C​(p.Glu1050Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.656
• Publications: 0 publications found

Genes affected

BRD8 (HGNC:19874): (bromodomain containing 8) The protein encoded by this gene interacts with thyroid hormone receptor in a ligand-dependent manner and enhances thyroid hormone-dependent activation from thyroid response elements. This protein contains a bromodomain and is thought to be a nuclear receptor coactivator. Multiple alternatively spliced transcript variants that encode distinct isoforms have been identified. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1131956).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139199.2. 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
	BRD8	NM_139199.2	MANE Select	c.3148G>C	p.Glu1050Gln	missense	Exon 23 of 27	NP_631938.2	Q9H0E9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD8	ENST00000254900.10	TSL:1 MANE Select	c.3148G>C	p.Glu1050Gln	missense	Exon 23 of 27	ENSP00000254900.5	Q9H0E9-1
	BRD8	ENST00000427976.1	TSL:3	c.466G>C	p.Glu156Gln	missense	Exon 3 of 6	ENSP00000392646.1	H7C026

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725154

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 43592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110870

Other (OTH) AF: 0.00 AC: 0 AN: 60216

GnomAD4 genome Cov.: 31

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	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.66
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.060
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.20		Loss of phosphorylation at S1047 (P = 0.1174)
MVP		0.32
MPC		0.12
ClinPred		0.32	T
GERP RS		1.2
Varity_R		0.076
gMVP		0.25
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr5-137485459;