chr3-52563648-G-A

Position:

• chr3-52563648-G-A

Variant summary

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

The ENST00000707071.1(PBRM1):​c.3921-155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,386 control chromosomes in the GnomAD database, including 9,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9503 hom., cov: 30)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.954

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=-0.87).
• BP6: Variant 3-52563648-G-A is Benign according to our data. Variant chr3-52563648-G-A is described in ClinVar as [Benign]. Clinvar id is 1244757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3921-155C>T		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.4098-155C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3921-155C>T		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50371 AN: 151268 Hom.: 9498 Cov.: 30

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.333 AC: 50396 AN: 151386 Hom.: 9503 Cov.: 30 AF XY: 0.335 AC XY: 24734 AN XY: 73906

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.364

Alfa AF: 0.371 Hom.: 2622

Bravo AF: 0.333

Asia WGS AF: 0.343 AC: 1190 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	-0.87
CADD	Benign	14
DANN	Benign	0.61

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: rs2289249; hg19: chr3-52597664; COSMIC: COSV56292167; COSMIC: COSV56292167;