NM_001003694.2:c.*842T>C

Variant names:

• chr3-9748191-T-C
• rs159153
• NM_001003694.2:c.*842T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003694.2(BRPF1):​c.*842T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,150 control chromosomes in the GnomAD database, including 7,953 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 0.32 (7953 hom., cov: 33)
• Consequence: BRPF1 NM_001003694.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 29 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
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRPF1	NM_001003694.2	MANE Select	c.*842T>C		downstream_gene	N/A	NP_001003694.1	P55201-2
	BRPF1	NM_001437892.1		c.*842T>C		downstream_gene	N/A	NP_001424821.1	A0A804HI52
	BRPF1	NM_001438342.1		c.*842T>C		downstream_gene	N/A	NP_001425271.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRPF1	ENST00000383829.7	TSL:1 MANE Select	c.*842T>C		downstream_gene	N/A	ENSP00000373340.2	P55201-2
	BRPF1	ENST00000424362.7	TSL:1	c.*842T>C		downstream_gene	N/A	ENSP00000398863.2	A0A8C8KWW5
	BRPF1	ENST00000919141.1		c.*842T>C		downstream_gene	N/A	ENSP00000589200.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48394 AN: 152032 Hom.: 7911 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48503 AN: 152150 Hom.: 7953 Cov.: 33 AF XY: 0.319 AC XY: 23741 AN XY: 74384

African (AFR) AF: 0.359 AC: 14874 AN: 41486

American (AMR) AF: 0.356 AC: 5442 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.0962 AC: 498 AN: 5178

South Asian (SAS) AF: 0.266 AC: 1286 AN: 4828

European-Finnish (FIN) AF: 0.317 AC: 3360 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21233 AN: 67986

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.314 Hom.: 4859

Bravo AF: 0.318

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.7
DANN	Benign	0.54
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs159153; hg19: chr3-9789875;