dbSNP rs2269112: BRPF1:c.3479+30C>T (chr3-9746484-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001003694.2(BRPF1):c.3479+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,531,202 control chromosomes in the GnomAD database, including 23,023 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 0.13 ( 1582 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21441 hom. )

Consequence

BRPF1
NM_001003694.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.86

Publications

22 publications found

Variant links:

Genes affected

BRPF1 (HGNC:14255): (bromodomain and PHD finger containing 1) This gene encodes a bromodomain, PHD finger and chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain containing protein. The encoded protein is a component of the MOZ/MORF histone acetyltransferase complexes which function as a transcriptional regulators. This protein binds to the catalytic MYST domains of the MOZ and MORF proteins and may play a role in stimulating acetyltransferase and transcriptional activity of the complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

BRPF1 Gene-Disease associations (from GenCC):

intellectual developmental disorder with dysmorphic facies and ptosis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Illumina
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

BRPF1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001003694.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003694.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRPF1	NM_001003694.2	MANE Select	c.3479+30C>T	intron	N/A	NP_001003694.1	P55201-2
BRPF1	NM_001437892.1		c.3563+30C>T	intron	N/A	NP_001424821.1	A0A804HI52
BRPF1	NM_001438342.1		c.3560+30C>T	intron	N/A	NP_001425271.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRPF1	ENST00000383829.7	TSL:1 MANE Select	c.3479+30C>T	intron	N/A	ENSP00000373340.2	P55201-2
BRPF1	ENST00000424362.7	TSL:1	c.3476+30C>T	intron	N/A	ENSP00000398863.2	A0A8C8KWW5
BRPF1	ENST00000919141.1		c.3581+30C>T	intron	N/A	ENSP00000589200.1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19595

AN:

152076

Hom.:

1586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0367

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.162

AC:

32902

AN:

203552

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.0316

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.172

AC:

236696

AN:

1379008

Hom.:

21441

Cov.:

AF XY:

0.174

AC XY:

118037

AN XY:

677850

show subpopulations

African (AFR)

AF:

0.0315

AC:

986

AN:

31294

American (AMR)

AF:

0.160

AC:

6017

AN:

37580

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

3829

AN:

22310

East Asian (EAS)

AF:

0.167

AC:

6306

AN:

37654

South Asian (SAS)

AF:

0.252

AC:

19087

AN:

75752

European-Finnish (FIN)

AF:

0.107

AC:

5382

AN:

50364

Middle Eastern (MID)

AF:

0.251

AC:

1348

AN:

5364

European-Non Finnish (NFE)

AF:

0.173

AC:

184070

AN:

1062252

Other (OTH)

AF:

0.171

AC:

9671

AN:

56438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

9017

18034

27052

36069

45086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6880

13760

20640

27520

34400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.129

AC:

19580

AN:

152194

Hom.:

1582

Cov.:

AF XY:

0.127

AC XY:

9446

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0366

AC:

1520

AN:

41538

American (AMR)

AF:

0.146

AC:

2228

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3464

East Asian (EAS)

AF:

0.174

AC:

902

AN:

5178

South Asian (SAS)

AF:

0.248

AC:

1197

AN:

4820

European-Finnish (FIN)

AF:

0.107

AC:

1139

AN:

10600

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11504

AN:

67986

Other (OTH)

AF:

0.140

AC:

295

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

865

1730

2595

3460

4325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

3502

Bravo

AF:

0.126

Asia WGS

AF:

0.178

AC:

617

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.99

(source)

DANN

Benign

0.74

PhyloP100

-3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over