6-32980830-C-T

Variant names:

• chr6-32980830-C-T
• rs1049414
• ENST00000482914.5:n.*2166C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000482914.5(BRD2):​n.*2166C>T variant causes a non coding transcript exon 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 ENST00000482914.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 9 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=-0.85).
• 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

African (AFR) AF: 0.543 AC: 13757 AN: 25344

American (AMR) AF: 0.630 AC: 22448 AN: 35622

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 16632 AN: 20670

East Asian (EAS) AF: 0.700 AC: 25393 AN: 36284

South Asian (SAS) AF: 0.742 AC: 52575 AN: 70896

European-Finnish (FIN) AF: 0.757 AC: 28135 AN: 37150

Middle Eastern (MID) AF: 0.736 AC: 2514 AN: 3414

European-Non Finnish (NFE) AF: 0.634 AC: 530285 AN: 836262

Other (OTH) AF: 0.655 AC: 31753 AN: 48502

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

African (AFR) AF: 0.515 AC: 21351 AN: 41422

American (AMR) AF: 0.637 AC: 9731 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3472

East Asian (EAS) AF: 0.657 AC: 3391 AN: 5158

South Asian (SAS) AF: 0.744 AC: 3579 AN: 4808

European-Finnish (FIN) AF: 0.770 AC: 8157 AN: 10594

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44029 AN: 67874

Other (OTH) AF: 0.629 AC: 1327 AN: 2110

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
PhyloP100		0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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