chr3-9744393-G-C

Variant names:

• chr3-9744393-G-C
• rs1559666507
• NM_001003694.2:c.2805G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001003694.2(BRPF1):​c.2805G>C​(p.Gly935Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,022 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: 0.0000027 (0 hom.)
• Consequence: BRPF1 NM_001003694.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.223 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF1	NM_001003694.2	c.2805G>C	p.Gly935Gly	synonymous_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.2805G>C	p.Gly935Gly	synonymous_variant	Exon 9 of 14	1	NM_001003694.2	ENSP00000373340.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235928 AF XY: 0.00

Gnomad AFR exome AF: 0.0000686

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000274 AC: 4 AN: 1458022 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725260

African (AFR) AF: 0.0000900 AC: 3 AN: 33336

American (AMR) AF: 0.0000226 AC: 1 AN: 44234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110066

Other (OTH) AF: 0.00 AC: 0 AN: 60104

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.1
DANN	Benign	0.59

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: rs1559666507; hg19: chr3-9786077; COSMIC: COSV57402949; COSMIC: COSV57402949;