3-52587611-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000707071.1(PBRM1):c.3011-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 859,722 control chromosomes in the GnomAD database, including 77,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (15638 hom., cov: 23)
  • Exomes 𝑓: 0.41 (61964 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-52587611-C-T is Benign according to our data. Variant chr3-52587611-C-T is described in ClinVar as [Benign]. Clinvar id is 1255178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3011-101G>A		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3188-101G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3011-101G>A		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 67312 AN: 147792 Hom.: 15621 Cov.: 23

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.407 AC: 289391 AN: 711834 Hom.: 61964 AF XY: 0.401 AC XY: 146569 AN XY: 365118

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.456 AC: 67374 AN: 147888 Hom.: 15638 Cov.: 23 AF XY: 0.456 AC XY: 32739 AN XY: 71872

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.458

Alfa AF: 0.319 Hom.: 850

Bravo AF: 0.470

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.4
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3733046; hg19: chr3-52621627;