rs3755806

Positions:

• chr3-52609669-T-C

Variant summary

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

The ENST00000707071.1(PBRM1):​c.2256A>G​(p.Thr752=) 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 1,612,182 control chromosomes in the GnomAD database, including 121,880 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 (9940 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111940 hom.)
• Consequence: PBRM1 ENST00000707071.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBRM1	NM_001405607.1	c.2256A>G	p.Thr752=	synonymous_variant	18/32	ENST00000707071.1	NP_001392536.1
PBRM1	NR_175959.1	n.2433A>G		non_coding_transcript_exon_variant	18/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.2256A>G	p.Thr752=	synonymous_variant	18/32		NM_001405607.1	ENSP00000516722	A1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52083 AN: 152036 Hom.: 9935 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.391 AC: 97976 AN: 250684 Hom.: 20376 AF XY: 0.383 AC XY: 51854 AN XY: 135476

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.533

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.427

Gnomad SAS exome AF: 0.240

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.386 AC: 564254 AN: 1460028 Hom.: 111940 Cov.: 33 AF XY: 0.382 AC XY: 277571 AN XY: 726406

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.342 AC: 52108 AN: 152154 Hom.: 9940 Cov.: 32 AF XY: 0.345 AC XY: 25637 AN XY: 74378

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.369

Alfa AF: 0.392 Hom.: 19644

Bravo AF: 0.342

Asia WGS AF: 0.346 AC: 1203 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	-0.61
CADD	Benign	5.5
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs3755806; hg19: chr3-52643685; COSMIC: COSV56259469; COSMIC: COSV56259469;