rs3918149

chr6-32968596-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.-1765G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,992 control chromosomes in the GnomAD database, including 1,303 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 0.12 (1297 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6 hom.)
• Consequence: BRD2 NM_005104.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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]

HLA-DMA (HGNC:4934): (major histocompatibility complex, class II, DM alpha) HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD2	NM_005104.4	c.-1765G>A		5_prime_UTR_variant	1/13	ENST00000374825.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD2	ENST00000374825.9	c.-1765G>A		5_prime_UTR_variant	1/13	1	NM_005104.4	P2
HLA-DMA	ENST00000422832.1	c.-12+406C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17895 AN: 152096 Hom.: 1289 Cov.: 33

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.125 AC: 97 AN: 778 Hom.: 6 Cov.: 0 AF XY: 0.112 AC XY: 67 AN XY: 598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.118 AC: 17900 AN: 152214 Hom.: 1297 Cov.: 33 AF XY: 0.121 AC XY: 8988 AN XY: 74426

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.134

Alfa AF: 0.118 Hom.: 923

Bravo AF: 0.119

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.3
Dann	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3918149; hg19: chr6-32936373; COSMIC: COSV66374648;