NM_005104.4:c.1200+33G>A

Variant names:

• chr6-32976969-G-A
• rs11908
• NM_005104.4:c.1200+33G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.1200+33G>A		intron_variant	Intron 7 of 12	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.1200+33G>A		intron_variant	Intron 7 of 12	1	NM_005104.4	ENSP00000363958.4

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

GnomAD2 exomes AF: 0.344 AC: 73767 AN: 214648 AF XY: 0.347

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 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

African (AFR) AF: 0.192 AC: 6182 AN: 32174

American (AMR) AF: 0.282 AC: 11328 AN: 40240

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 7998 AN: 23568

East Asian (EAS) AF: 0.213 AC: 8380 AN: 39272

South Asian (SAS) AF: 0.318 AC: 25789 AN: 81020

European-Finnish (FIN) AF: 0.513 AC: 25838 AN: 50400

Middle Eastern (MID) AF: 0.340 AC: 1886 AN: 5550

European-Non Finnish (NFE) AF: 0.360 AC: 392245 AN: 1090658

Other (OTH) AF: 0.325 AC: 19010 AN: 58528

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

African (AFR) AF: 0.201 AC: 8361 AN: 41496

American (AMR) AF: 0.282 AC: 4310 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.191 AC: 988 AN: 5182

South Asian (SAS) AF: 0.313 AC: 1511 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5444 AN: 10558

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25578 AN: 67982

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.352 Hom.: 39760

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
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11908; hg19: chr6-32944746; COSMIC: COSV66373354; COSMIC: COSV66373354;