6-32980830-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005104.4(BRD2):​c.*112C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000895 in 1,116,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: BRD2 NM_005104.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.*112C>A		3_prime_UTR	Exon 13 of 13	NP_005095.1	P25440-1
	BRD2	NM_001199455.1		c.*112C>A		3_prime_UTR	Exon 13 of 13	NP_001186384.1	P25440-2
	BRD2	NM_001113182.3		c.*112C>A		3_prime_UTR	Exon 13 of 13	NP_001106653.1	P25440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD2	ENST00000374825.9	TSL:1 MANE Select	c.*112C>A		3_prime_UTR	Exon 13 of 13	ENSP00000363958.4	P25440-1
	BRD2	ENST00000395287.5	TSL:1	c.*112C>A		3_prime_UTR	Exon 13 of 13	ENSP00000378702.1	P25440-2
	BRD2	ENST00000449025.5	TSL:1	c.*112C>A		3_prime_UTR	Exon 12 of 12	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.95e-7 AC: 1 AN: 1116840 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 560290

African (AFR) AF: 0.00 AC: 0 AN: 25758

American (AMR) AF: 0.00 AC: 0 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20708

East Asian (EAS) AF: 0.00 AC: 0 AN: 36322

South Asian (SAS) AF: 0.00 AC: 0 AN: 71068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3426

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838036

Other (OTH) AF: 0.00 AC: 0 AN: 48632

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.45
PhyloP100		0.086
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

Other links and lift over

dbSNP: rs1049414; hg19: chr6-32948607;