rs11750814

Variant names:

• chr5-138164976-G-A
• rs11750814
• NM_139199.2:c.1469C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-138164976-G-A
• chr5-138164976-G-C
• chr5-138164976-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139199.2(BRD8):​c.1469C>T​(p.Thr490Met) variant causes a missense change. The variant allele was found at a frequency of 0.169 in 1,613,960 control chromosomes in the GnomAD database, including 24,967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T490A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1641 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23326 hom.)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98
• Publications: 38 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015330613).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

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.1469C>T	p.Thr490Met	missense	Exon 12 of 27	NP_631938.2	Q9H0E9-1
	BRD8	NM_006696.5		c.1688C>T	p.Thr563Met	missense	Exon 13 of 22	NP_006687.3
	BRD8	NM_001164326.2		c.1478C>T	p.Thr493Met	missense	Exon 12 of 20	NP_001157798.1	Q9H0E9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD8	ENST00000254900.10	TSL:1 MANE Select	c.1469C>T	p.Thr490Met	missense	Exon 12 of 27	ENSP00000254900.5	Q9H0E9-1
	BRD8	ENST00000230901.9	TSL:1	c.1688C>T	p.Thr563Met	missense	Exon 13 of 22	ENSP00000230901.5	Q9H0E9-2
	BRD8	ENST00000454473.5	TSL:5	c.1556C>T	p.Thr519Met	missense	Exon 13 of 21	ENSP00000398067.1	H7C127

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20362 AN: 151960 Hom.: 1643 Cov.: 32

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.148 AC: 37120 AN: 251362 AF XY: 0.154

Gnomad AFR exome AF: 0.0733

Gnomad AMR exome AF: 0.0852

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0113

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.172 AC: 252118 AN: 1461882 Hom.: 23326 Cov.: 33 AF XY: 0.174 AC XY: 126464 AN XY: 727244

African (AFR) AF: 0.0686 AC: 2298 AN: 33480

American (AMR) AF: 0.0873 AC: 3904 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2732 AN: 26136

East Asian (EAS) AF: 0.0107 AC: 425 AN: 39700

South Asian (SAS) AF: 0.216 AC: 18639 AN: 86258

European-Finnish (FIN) AF: 0.183 AC: 9793 AN: 53420

Middle Eastern (MID) AF: 0.0917 AC: 529 AN: 5768

European-Non Finnish (NFE) AF: 0.184 AC: 204464 AN: 1112002

Other (OTH) AF: 0.155 AC: 9334 AN: 60396

GnomAD4 genome AF: 0.134 AC: 20357 AN: 152078 Hom.: 1641 Cov.: 32 AF XY: 0.133 AC XY: 9916 AN XY: 74328

African (AFR) AF: 0.0725 AC: 3009 AN: 41510

American (AMR) AF: 0.0911 AC: 1390 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3472

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5182

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4808

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10556

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12207 AN: 67972

Other (OTH) AF: 0.120 AC: 253 AN: 2112

Alfa AF: 0.157 Hom.: 7136

Bravo AF: 0.122

TwinsUK AF: 0.184 AC: 683

ALSPAC AF: 0.181 AC: 699

ESP6500AA AF: 0.0824 AC: 363

ESP6500EA AF: 0.174 AC: 1496

ExAC AF: 0.152 AC: 18453

Asia WGS AF: 0.130 AC: 453 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.037	D
Sift4G	Uncertain	0.046	D
Polyphen		0.99	D
Vest4		0.11
MPC		0.41
ClinPred		0.028	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.30
Mutation Taster		=98/2	polymorphism (auto)

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: rs11750814; hg19: chr5-137500665; COSMIC: COSV50153597; COSMIC: COSV50153597;