3-52564343-T-C

Variant summary

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

The ENST00000707071.1(PBRM1):c.3737-110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 820,578 control chromosomes in the GnomAD database, including 1,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (958 hom., cov: 31)
  • Exomes 𝑓: 0.025 (608 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.900

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-52564343-T-C is Benign according to our data. Variant chr3-52564343-T-C is described in ClinVar as [Benign]. Clinvar id is 1282950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3737-110A>G		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3914-110A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3737-110A>G		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11015 AN: 152100 Hom.: 952 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0250 AC: 16726 AN: 668360 Hom.: 608 AF XY: 0.0248 AC XY: 8742 AN XY: 352248

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.0268

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.000186

Gnomad4 SAS exome AF: 0.0366

Gnomad4 FIN exome AF: 0.00590

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0726 AC: 11052 AN: 152218 Hom.: 958 Cov.: 31 AF XY: 0.0709 AC XY: 5276 AN XY: 74424

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.00584

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0531 Hom.: 86

Bravo AF: 0.0824

Asia WGS AF: 0.0280 AC: 100 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 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.42
Dann	Benign	0.60

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: rs1987234; hg19: chr3-52598359;