NM_001003694.2:c.1854+237C>T

Variant names:

• chr3-9741676-C-T
• rs159154
• NM_001003694.2:c.1854+237C>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.1854+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 149,502 control chromosomes in the GnomAD database, including 5,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.27 (5811 hom., cov: 30)
• Consequence: BRPF1 NM_001003694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 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.1854+237C>T		intron	N/A	NP_001003694.1	P55201-2
	BRPF1	NM_001437892.1		c.1854+237C>T		intron	N/A	NP_001424821.1	A0A804HI52
	BRPF1	NM_001438342.1		c.1854+237C>T		intron	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.1854+237C>T		intron	N/A	ENSP00000373340.2	P55201-2
	BRPF1	ENST00000424362.7	TSL:1	c.1854+237C>T		intron	N/A	ENSP00000398863.2	A0A8C8KWW5
	BRPF1	ENST00000919141.1		c.1854+237C>T		intron	N/A	ENSP00000589200.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 40678 AN: 149448 Hom.: 5791 Cov.: 30

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.273 AC: 40740 AN: 149502 Hom.: 5811 Cov.: 30 AF XY: 0.272 AC XY: 19738 AN XY: 72620

African (AFR) AF: 0.275 AC: 11203 AN: 40694

American (AMR) AF: 0.221 AC: 3309 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3456

East Asian (EAS) AF: 0.0890 AC: 452 AN: 5076

South Asian (SAS) AF: 0.207 AC: 982 AN: 4750

European-Finnish (FIN) AF: 0.321 AC: 3076 AN: 9570

Middle Eastern (MID) AF: 0.184 AC: 52 AN: 282

European-Non Finnish (NFE) AF: 0.297 AC: 20088 AN: 67672

Other (OTH) AF: 0.274 AC: 573 AN: 2088

Alfa AF: 0.286 Hom.: 3339

Bravo AF: 0.261

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.61
PhyloP100		-0.54
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: rs159154; hg19: chr3-9783360;