NM_001003694.2:c.3479+30C>T

Variant names:

• chr3-9746484-C-T
• rs2269112
• NM_001003694.2:c.3479+30C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF1	NM_001003694.2	c.3479+30C>T		intron_variant	Intron 13 of 13	ENST00000383829.7	NP_001003694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRPF1	ENST00000383829.7	c.3479+30C>T		intron_variant	Intron 13 of 13	1	NM_001003694.2	ENSP00000373340.2

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

GnomAD2 exomes AF: 0.162 AC: 32902 AN: 203552 AF XY: 0.167

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

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

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

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: 81 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11504 AN: 67986

Other (OTH) AF: 0.140 AC: 295 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
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)

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