5-138145841-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139199.2(BRD8):​c.3316T>G​(p.Leu1106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,613,976 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (93 hom.)
• Consequence: BRD8 NM_139199.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.730
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018951297).
• BP6: Variant 5-138145841-A-C is Benign according to our data. Variant chr5-138145841-A-C is described in ClinVar as Benign. ClinVar VariationId is 783395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 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.3316T>G	p.Leu1106Val	missense	Exon 24 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.3316T>G	p.Leu1106Val	missense	Exon 24 of 27	ENSP00000254900.5	Q9H0E9-1
	BRD8	ENST00000427976.1	TSL:3	c.634T>G	p.Leu212Val	missense	Exon 4 of 6	ENSP00000392646.1	H7C026

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2677 AN: 152144 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00442

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00752 AC: 1891 AN: 251386 AF XY: 0.00660

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00512

Gnomad OTH exome AF: 0.00734

GnomAD4 exome AF: 0.00509 AC: 7438 AN: 1461714 Hom.: 93 Cov.: 30 AF XY: 0.00503 AC XY: 3659 AN XY: 727158

African (AFR) AF: 0.0567 AC: 1897 AN: 33460

American (AMR) AF: 0.00389 AC: 174 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0224 AC: 586 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39678

South Asian (SAS) AF: 0.00259 AC: 223 AN: 86254

European-Finnish (FIN) AF: 0.000880 AC: 47 AN: 53394

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5766

European-Non Finnish (NFE) AF: 0.00353 AC: 3921 AN: 1111924

Other (OTH) AF: 0.00778 AC: 470 AN: 60386

GnomAD4 genome AF: 0.0176 AC: 2681 AN: 152262 Hom.: 53 Cov.: 32 AF XY: 0.0166 AC XY: 1235 AN XY: 74456

African (AFR) AF: 0.0512 AC: 2128 AN: 41538

American (AMR) AF: 0.00791 AC: 121 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4824

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00443 AC: 301 AN: 68020

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0100 Hom.: 45

Bravo AF: 0.0201

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.0513 AC: 226

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00846 AC: 1027

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00682

EpiControl AF: 0.00741

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.73
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.012
Sift	Benign	0.086	T
Sift4G	Uncertain	0.055	T
Polyphen		0.44	B
Vest4		0.30
MVP		0.18
MPC		0.13
ClinPred		0.019	T
GERP RS		2.9
Varity_R		0.064
gMVP		0.15
Mutation Taster		=96/4	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: rs79921495; hg19: chr5-137481530; COSMIC: COSV99068928;