chr3-52609669-T-C

Variant names:

• chr3-52609669-T-C
• rs3755806
• NM_001405607.1:c.2256A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001405607.1(PBRM1):​c.2256A>G​(p.Thr752Thr) 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 NM_001405607.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 56 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PBRM1	NM_001405607.1	c.2256A>G	p.Thr752Thr	synonymous_variant	Exon 18 of 32	ENST00000707071.1	NP_001392536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.2256A>G	p.Thr752Thr	synonymous_variant	Exon 18 of 32		NM_001405607.1	ENSP00000516722.1

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

GnomAD2 exomes AF: 0.391 AC: 97976 AN: 250684 AF XY: 0.383

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 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

African (AFR) AF: 0.166 AC: 5548 AN: 33460

American (AMR) AF: 0.519 AC: 23155 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 12055 AN: 26090

East Asian (EAS) AF: 0.476 AC: 18907 AN: 39682

South Asian (SAS) AF: 0.240 AC: 20681 AN: 86128

European-Finnish (FIN) AF: 0.403 AC: 21512 AN: 53400

Middle Eastern (MID) AF: 0.406 AC: 2336 AN: 5758

European-Non Finnish (NFE) AF: 0.394 AC: 437908 AN: 1110622

Other (OTH) AF: 0.367 AC: 22152 AN: 60308

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

African (AFR) AF: 0.177 AC: 7327 AN: 41496

American (AMR) AF: 0.463 AC: 7075 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1565 AN: 3466

East Asian (EAS) AF: 0.429 AC: 2220 AN: 5180

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4830

European-Finnish (FIN) AF: 0.392 AC: 4154 AN: 10586

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27297 AN: 68000

Other (OTH) AF: 0.369 AC: 777 AN: 2106

Alfa AF: 0.388 Hom.: 24921

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
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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