5-138145841-A-T

Variant names:

• chr5-138145841-A-T
• rs79921495
• NM_139199.2:c.3316T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139199.2(BRD8):​c.3316T>A​(p.Leu1106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12159675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD8	NM_139199.2	c.3316T>A	p.Leu1106Met	missense_variant	Exon 24 of 27	ENST00000254900.10	NP_631938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD8	ENST00000254900.10	c.3316T>A	p.Leu1106Met	missense_variant	Exon 24 of 27	1	NM_139199.2	ENSP00000254900.5
BRD8	ENST00000427976.1	c.634T>A	p.Leu212Met	missense_variant	Exon 4 of 6	3		ENSP00000392646.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.077
Sift	Benign	0.043	D;D
Sift4G	Uncertain	0.060	T;T
Polyphen		0.98	D;.
Vest4		0.22
MutPred		0.38		Gain of methylation at K1109 (P = 0.0698);.;
MVP		0.22
MPC		0.26
ClinPred		0.74	D
GERP RS		2.9
Varity_R		0.090
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs79921495; hg19: chr5-137481530;