chr3-52589449-A-T

Position:

• chr3-52589449-A-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.2825-194T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,322 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (360 hom., cov: 31)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.15

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=-0.85).
• BP6: Variant 3-52589449-A-T is Benign according to our data. Variant chr3-52589449-A-T is described in ClinVar as [Benign]. Clinvar id is 1292739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.2825-194T>A		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3002-194T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.2825-194T>A		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9113 AN: 152204 Hom.: 360 Cov.: 31

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0721

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

GnomAD4 genome AF: 0.0598 AC: 9111 AN: 152322 Hom.: 360 Cov.: 31 AF XY: 0.0569 AC XY: 4235 AN XY: 74480

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.0718

Alfa AF: 0.0663 Hom.: 54

Bravo AF: 0.0600

Asia WGS AF: 0.0480 AC: 166 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.48

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: rs35225119; hg19: chr3-52623465;