6-32980830-C-T

Variant names:

• chr6-32980830-C-T
• rs1049414
• NM_005104.4:c.*112C>T

Variant summary

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

The NM_005104.4(BRD2):​c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,266,074 control chromosomes in the GnomAD database, including 266,746 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 0.63 (30409 hom., cov: 31)
  • Exomes 𝑓: 0.65 (236337 hom.)
• Consequence: BRD2 NM_005104.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD2	NM_005104.4	c.*112C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000374825.9	NP_005095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD2	ENST00000374825.9	c.*112C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_005104.4	ENSP00000363958.4

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95087 AN: 151818 Hom.: 30393 Cov.: 31

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.649 AC: 723492 AN: 1114144 Hom.: 236337 Cov.: 15 AF XY: 0.655 AC XY: 366252 AN XY: 559010

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.634

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.626 AC: 95139 AN: 151930 Hom.: 30409 Cov.: 31 AF XY: 0.635 AC XY: 47159 AN XY: 74274

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.629

Alfa AF: 0.558 Hom.: 1717

Bravo AF: 0.606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1049414; hg19: chr6-32948607; COSMIC: COSV66373014; COSMIC: COSV66373014;