3-52586729-G-A

Position:

• chr3-52586729-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000707071.1(PBRM1):​c.3169-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (230 hom., cov: 19)
  • Exomes 𝑓: 0.036 (173 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-52586729-G-A is Benign according to our data. Variant chr3-52586729-G-A is described in ClinVar as [Benign]. Clinvar id is 1292831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3169-41C>T		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3346-41C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3169-41C>T		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 5624 AN: 78024 Hom.: 228 Cov.: 19

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.000732

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0763

GnomAD3 exomes AF: 0.0251 AC: 2937 AN: 116936 Hom.: 86 AF XY: 0.0236 AC XY: 1553 AN XY: 65842

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.000131

Gnomad SAS exome AF: 0.0361

Gnomad FIN exome AF: 0.00742

Gnomad NFE exome AF: 0.0194

Gnomad OTH exome AF: 0.0271

GnomAD4 exome AF: 0.0363 AC: 11327 AN: 312018 Hom.: 173 Cov.: 8 AF XY: 0.0350 AC XY: 5649 AN XY: 161624

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.000235

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.00967

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0722 AC: 5639 AN: 78088 Hom.: 230 Cov.: 19 AF XY: 0.0727 AC XY: 2677 AN XY: 36804

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.000732

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0333

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0466 Hom.: 44

Bravo AF: 0.0487

Asia WGS AF: 0.0200 AC: 71 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.1
DANN	Benign	0.70

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: rs80314598; hg19: chr3-52620745;