rs2590838

Positions:

• chr3-52588070-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707071.1(PBRM1):​c.3011-560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,870 control chromosomes in the GnomAD database, including 23,019 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 0.54 (23019 hom., cov: 30)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBRM1	NM_001405607.1	c.3011-560C>T		intron_variant		ENST00000707071.1	NP_001392536.1
PBRM1	NR_175959.1	n.3188-560C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.3011-560C>T		intron_variant			NM_001405607.1	ENSP00000516722	A1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82519 AN: 151752 Hom.: 22992 Cov.: 30

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82604 AN: 151870 Hom.: 23019 Cov.: 30 AF XY: 0.539 AC XY: 39987 AN XY: 74208

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.550

Alfa AF: 0.519 Hom.: 38037

Bravo AF: 0.563

Asia WGS AF: 0.435 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.88
DANN	Benign	0.28

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: rs2590838; hg19: chr3-52622086;