rs2269112

Positions:

• chr3-9746484-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRPF1	NM_001003694.2	c.3479+30C>T		intron_variant		ENST00000383829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRPF1	ENST00000383829.7	c.3479+30C>T		intron_variant		1	NM_001003694.2	A1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19595 AN: 152076 Hom.: 1586 Cov.: 32

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

GnomAD3 exomes AF: 0.162 AC: 32902 AN: 203552 Hom.: 2956 AF XY: 0.167 AC XY: 18261 AN XY: 109172

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 SAS exome AF: 0.257

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.: 31 AF XY: 0.174 AC XY: 118037 AN XY: 677850

Gnomad4 AFR exome AF: 0.0315

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.129 AC: 19580 AN: 152194 Hom.: 1582 Cov.: 32 AF XY: 0.127 AC XY: 9446 AN XY: 74390

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.140

Alfa AF: 0.160 Hom.: 2929

Bravo AF: 0.126

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2269112; hg19: chr3-9788168; COSMIC: COSV57353271; COSMIC: COSV57353271;