3-52550771-T-C

Variant names:

• chr3-52550771-T-C
• rs2251219
• ENST00000707071.1:c.4701A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001405601.1(PBRM1):​c.4701A>G​(p.Pro1567Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,608,634 control chromosomes in the GnomAD database, including 121,663 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 (9946 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111717 hom.)
• Consequence: PBRM1 NM_001405601.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.181 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBRM1	NM_001405601.1	c.4701A>G	p.Pro1567Pro	synonymous_variant	Exon 30 of 32		NP_001392530.1
PBRM1	NM_001405607.1	c.4701A>G	p.Pro1567Pro	synonymous_variant	Exon 30 of 32		NP_001392536.1
PBRM1	NM_001405598.1	c.4683A>G	p.Pro1561Pro	synonymous_variant	Exon 29 of 31		NP_001392527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.4701A>G	p.Pro1567Pro	synonymous_variant	Exon 30 of 32			ENSP00000516722.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52057 AN: 152050 Hom.: 9938 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.391 AC: 98014 AN: 250648 Hom.: 20386 AF XY: 0.383 AC XY: 51841 AN XY: 135436

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.427

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.386 AC: 562397 AN: 1456466 Hom.: 111717 Cov.: 30 AF XY: 0.382 AC XY: 276893 AN XY: 724932

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.342 AC: 52085 AN: 152168 Hom.: 9946 Cov.: 32 AF XY: 0.344 AC XY: 25613 AN XY: 74386

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.370

Alfa AF: 0.396 Hom.: 30901

Bravo AF: 0.342

Asia WGS AF: 0.355 AC: 1234 AN: 3478

EpiCase AF: 0.412

EpiControl AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.8
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2251219; hg19: chr3-52584787; COSMIC: COSV56259388; COSMIC: COSV56259388;