rs757645490

Variant names:

• chr3-9744256-C-T
• rs757645490
• NM_001003694.2:c.2668C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003694.2(BRPF1):​c.2668C>T​(p.His890Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,426,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BRPF1 NM_001003694.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23833501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF1	NM_001003694.2	c.2668C>T	p.His890Tyr	missense_variant	Exon 9 of 14	ENST00000383829.7	NP_001003694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRPF1	ENST00000383829.7	c.2668C>T	p.His890Tyr	missense_variant	Exon 9 of 14	1	NM_001003694.2	ENSP00000373340.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000443 AC: 1 AN: 225588 Hom.: 0 AF XY: 0.00000815 AC XY: 1 AN XY: 122668

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426198 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 706252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000263

Gnomad4 ASJ exome AF: 0.0000412

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	.;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.92	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.78	P;P;P
Vest4		0.45
MutPred		0.22		.;.;Gain of phosphorylation at H884 (P = 0.0117);
MVP		0.33
MPC		0.74
ClinPred		0.48	T
GERP RS		5.8
Varity_R		0.12
gMVP		0.30

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: rs757645490; hg19: chr3-9785940;