3-52588070-G-A

Variant names:

• chr3-52588070-G-A
• rs2590838
• NM_001405607.1:c.3011-560C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001405601.1(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 NM_001405601.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 52 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405601.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.3011-560C>T		intron	N/A	NP_001392536.1
	PBRM1	NM_001405601.1		c.3011-560C>T		intron	N/A	NP_001392530.1
	PBRM1	NM_001405598.1		c.2993-560C>T		intron	N/A	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.3011-560C>T		intron	N/A	ENSP00000516722.1
	PBRM1	ENST00000296302.11	TSL:1	c.2966-560C>T		intron	N/A	ENSP00000296302.7
	PBRM1	ENST00000409114.7	TSL:1	c.3011-560C>T		intron	N/A	ENSP00000386643.3

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

African (AFR) AF: 0.641 AC: 26519 AN: 41380

American (AMR) AF: 0.608 AC: 9271 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1806 AN: 3470

East Asian (EAS) AF: 0.456 AC: 2357 AN: 5168

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4812

European-Finnish (FIN) AF: 0.464 AC: 4889 AN: 10536

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34490 AN: 67956

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.523 Hom.: 88409

Bravo AF: 0.563

Asia WGS AF: 0.435 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.88
DANN	Benign	0.28
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2590838; hg19: chr3-52622086;