ENST00000707071.1:c.3642A>T

Variant names:

• chr3-52576635-T-A
• rs17264436
• NM_001405607.1:c.3642A>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000707071.1(PBRM1):​c.3642A>T​(p.Pro1214Pro) 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
• Publications: 38 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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000707071.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.3642A>T	p.Pro1214Pro	synonymous	Exon 24 of 32	NP_001392536.1	A0A9L9PXL4
	PBRM1	NM_001405601.1		c.3642A>T	p.Pro1214Pro	synonymous	Exon 24 of 32	NP_001392530.1	A0A9L9PXL4
	PBRM1	NM_001405598.1		c.3624A>T	p.Pro1208Pro	synonymous	Exon 23 of 31	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.3642A>T	p.Pro1214Pro	synonymous	Exon 24 of 32	ENSP00000516722.1	A0A9L9PXL4
	PBRM1	ENST00000296302.11	TSL:1	c.3597A>T	p.Pro1199Pro	synonymous	Exon 22 of 30	ENSP00000296302.7	Q86U86-1
	PBRM1	ENST00000409114.7	TSL:1	c.3642A>T	p.Pro1214Pro	synonymous	Exon 23 of 30	ENSP00000386643.3	Q86U86-8

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

GnomAD2 exomes AF: 0.383 AC: 94839 AN: 247530 AF XY: 0.374

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 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

African (AFR) AF: 0.164 AC: 5480 AN: 33334

American (AMR) AF: 0.516 AC: 22601 AN: 43834

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11985 AN: 26046

East Asian (EAS) AF: 0.476 AC: 18757 AN: 39396

South Asian (SAS) AF: 0.214 AC: 18199 AN: 84898

European-Finnish (FIN) AF: 0.401 AC: 21402 AN: 53368

Middle Eastern (MID) AF: 0.399 AC: 2298 AN: 5758

European-Non Finnish (NFE) AF: 0.387 AC: 428982 AN: 1107964

Other (OTH) AF: 0.363 AC: 21807 AN: 60148

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

African (AFR) AF: 0.175 AC: 7275 AN: 41502

American (AMR) AF: 0.459 AC: 7008 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1559 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5176

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4814

European-Finnish (FIN) AF: 0.390 AC: 4104 AN: 10526

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26898 AN: 67998

Other (OTH) AF: 0.367 AC: 775 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		-0.33
Mutation Taster		=86/14	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: rs17264436; hg19: chr3-52610651; COSMIC: COSV56259420;