rs11908

chr6-32976969-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005104.4(BRD2):c.1200+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,573,522 control chromosomes in the GnomAD database, including 98,723 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.

• Frequency:
  • Genomes: 𝑓 0.32 (8408 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90315 hom.)
• Consequence: BRD2 NM_005104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

Genes affected

BRD2 (HGNC:1103): (bromodomain containing 2) This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD2	NM_005104.4	c.1200+33G>A		intron_variant		ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9	c.1200+33G>A		intron_variant		1	NM_005104.4	P2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48371 AN: 151994 Hom.: 8408 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.344 AC: 73767 AN: 214648 Hom.: 13420 AF XY: 0.347 AC XY: 40739 AN XY: 117338

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.333

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.351 AC: 498656 AN: 1421410 Hom.: 90315 Cov.: 39 AF XY: 0.352 AC XY: 247268 AN XY: 703018

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.513

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.318 AC: 48381 AN: 152112 Hom.: 8408 Cov.: 32 AF XY: 0.323 AC XY: 24024 AN XY: 74332

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.277

Alfa AF: 0.356 Hom.: 17240

Bravo AF: 0.291

Asia WGS AF: 0.240 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	18
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11908; hg19: chr6-32944746; COSMIC: COSV66373354; COSMIC: COSV66373354;