rs3918149

Variant names:

• chr6-32968596-G-A
• rs3918149
• NM_005104.4:c.-1765G>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.-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
• Publications: 19 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]

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]

LOC124901302 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005104.4. 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
	BRD2	NM_005104.4	MANE Select	c.-1765G>A		5_prime_UTR	Exon 1 of 13	NP_005095.1
	LOC124901302	NR_190903.1		n.-75C>T		upstream_gene	N/A
	LOC124901302	NR_190904.1		n.-75C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.-1765G>A		5_prime_UTR	Exon 1 of 13	ENSP00000363958.4
	HLA-DMA	ENST00000422832.1	TSL:6	c.-12+406C>T		intron	N/A	ENSP00000403122.1
	HLA-DMA	ENST00000464392.1	TSL:6	n.-152C>T		upstream_gene	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.0833 AC: 1 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.188 AC: 3 AN: 16

South Asian (SAS) AF: 0.188 AC: 15 AN: 80

European-Finnish (FIN) AF: 0.0667 AC: 2 AN: 30

Middle Eastern (MID) AF: 0.125 AC: 1 AN: 8

European-Non Finnish (NFE) AF: 0.112 AC: 65 AN: 580

Other (OTH) AF: 0.278 AC: 10 AN: 36

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

African (AFR) AF: 0.0636 AC: 2642 AN: 41548

American (AMR) AF: 0.185 AC: 2834 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5160

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7891 AN: 67972

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.115 Hom.: 2344

Bravo AF: 0.119

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		0.11
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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