rs17264436

chr3-52576635-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000707071.1(PBRM1):c.3642A>T(p.Pro1214=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,606,806 control chromosomes in the GnomAD database, including 117,513 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 0.34 (9705 hom., cov: 31)
  • Exomes 𝑓: 0.38 (107808 hom.)
• Consequence: PBRM1 ENST00000707071.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

Genes affected

PBRM1 (HGNC:30064): (polybromo 1) This locus encodes a subunit of ATP-dependent chromatin-remodeling complexes. The encoded protein has been identified as in integral component of complexes necessary for ligand-dependent transcriptional activation by nuclear hormone receptors. Mutations at this locus have been associated with primary clear cell renal cell carcinoma. [provided by RefSeq, Feb 2012]

UQCC5 (HGNC:37257): (ubiquinol-cytochrome c reductase complex assembly factor 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-0.334 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3642A>T	p.Pro1214=	synonymous_variant	24/32	ENST00000707071.1
PBRM1	NR_175959.1	n.3819A>T		non_coding_transcript_exon_variant	24/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3642A>T	p.Pro1214=	synonymous_variant	24/32		NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51392 AN: 151942 Hom.: 9698 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.361

GnomAD3 exomes AF: 0.383 AC: 94839 AN: 247530 Hom.: 19510 AF XY: 0.374 AC XY: 50145 AN XY: 133952

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.424

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.379 AC: 551511 AN: 1454746 Hom.: 107808 Cov.: 30 AF XY: 0.374 AC XY: 270929 AN XY: 723710

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.338 AC: 51421 AN: 152060 Hom.: 9705 Cov.: 31 AF XY: 0.340 AC XY: 25272 AN XY: 74300

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.367

Alfa AF: 0.388 Hom.: 3970

Bravo AF: 0.338

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	11
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17264436; hg19: chr3-52610651; COSMIC: COSV56259420;