NM_005104.4:c.1330-4G>C

Variant names:

• chr6-32977753-G-C
• rs3097644
• NM_005104.4:c.1330-4G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005104.4(BRD2):​c.1330-4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,612,886 control chromosomes in the GnomAD database, including 691,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68838 hom., cov: 32)
  • Exomes 𝑓: 0.92 (622981 hom.)
• Consequence: BRD2 NM_005104.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001595
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.20
• Publications: 22 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-32977753-G-C is Benign according to our data. Variant chr6-32977753-G-C is described in ClinVar as Benign. ClinVar VariationId is 95242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1330-4G>C		splice_region intron	N/A	NP_005095.1	P25440-1
	BRD2	NM_001199455.1		c.1330-4G>C		splice_region intron	N/A	NP_001186384.1	P25440-2
	BRD2	NM_001113182.3		c.1330-4G>C		splice_region intron	N/A	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.1330-4G>C		splice_region intron	N/A	ENSP00000363958.4	P25440-1
	BRD2	ENST00000395287.5	TSL:1	c.1330-4G>C		splice_region intron	N/A	ENSP00000378702.1	P25440-2
	BRD2	ENST00000449025.5	TSL:1	c.1345-4G>C		splice_region intron	N/A	ENSP00000409613.1	H0Y6K2

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144575 AN: 152182 Hom.: 68775 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.962

GnomAD2 exomes AF: 0.951 AC: 233590 AN: 245694 AF XY: 0.951

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.981

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 0.994

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.920

Gnomad OTH exome AF: 0.951

GnomAD4 exome AF: 0.923 AC: 1348012 AN: 1460586 Hom.: 622981 Cov.: 75 AF XY: 0.925 AC XY: 672457 AN XY: 726600

African (AFR) AF: 0.987 AC: 33053 AN: 33478

American (AMR) AF: 0.980 AC: 43822 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 25632 AN: 26116

East Asian (EAS) AF: 0.995 AC: 39488 AN: 39694

South Asian (SAS) AF: 0.990 AC: 85384 AN: 86254

European-Finnish (FIN) AF: 0.924 AC: 48298 AN: 52282

Middle Eastern (MID) AF: 0.989 AC: 5707 AN: 5768

European-Non Finnish (NFE) AF: 0.909 AC: 1010330 AN: 1111902

Other (OTH) AF: 0.932 AC: 56298 AN: 60374

GnomAD4 genome AF: 0.950 AC: 144697 AN: 152300 Hom.: 68838 Cov.: 32 AF XY: 0.951 AC XY: 70858 AN XY: 74480

African (AFR) AF: 0.984 AC: 40882 AN: 41548

American (AMR) AF: 0.977 AC: 14952 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 3403 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5147 AN: 5182

South Asian (SAS) AF: 0.990 AC: 4780 AN: 4830

European-Finnish (FIN) AF: 0.929 AC: 9864 AN: 10614

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62491 AN: 68026

Other (OTH) AF: 0.963 AC: 2035 AN: 2114

Alfa AF: 0.930 Hom.: 49163

Bravo AF: 0.955

Asia WGS AF: 0.985 AC: 3427 AN: 3478

EpiCase AF: 0.927

EpiControl AF: 0.930

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	BRD2-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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: rs3097644; hg19: chr6-32945530;