Variant 3-52554639-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000707071.1(PBRM1):c.4654+85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 1,220,390 control chromosomes in the GnomAD database, including 5,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 478 hom., cov: 32)

Exomes 𝑓: 0.090 ( 4719 hom. )

Consequence

PBRM1
ENST00000707071.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.92

Variant links:

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]

PBRM1 links:

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]

UQCC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-52554639-G-A is Benign according to our data. Variant chr3-52554639-G-A is described in ClinVar as [Benign]. Clinvar id is 1294143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1 linkuse as main transcript	c.4654+85C>T		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1 linkuse as main transcript	n.4666+85C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1 linkuse as main transcript	c.4654+85C>T		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10552

AN:

152114

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0628

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0811

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0937

Gnomad OTH

AF:

0.0703

GnomAD4 exome

AF:

0.0903

AC:

96443

AN:

1068158

Hom.:

4719

AF XY:

0.0910

AC XY:

48119

AN XY:

528492

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0472

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0863

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0945

Gnomad4 OTH exome

AF:

0.0878

GnomAD4 genome

AF:

0.0693

AC:

10548

AN:

152232

Hom.:

478

Cov.:

AF XY:

0.0711

AC XY:

5295

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0189

Gnomad4 AMR

AF:

0.0628

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0809

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0936

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0897

Hom.:

924

Bravo

AF:

0.0625

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over