3-52576399-T-C

Position:

• chr3-52576399-T-C

Variant summary

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

The ENST00000707071.1(PBRM1):​c.3736+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 506,190 control chromosomes in the GnomAD database, including 48,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15998 hom., cov: 30)
  • Exomes 𝑓: 0.42 (32186 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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=-0.97).
• BP6: Variant 3-52576399-T-C is Benign according to our data. Variant chr3-52576399-T-C is described in ClinVar as [Benign]. Clinvar id is 1273379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3736+142A>G		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3913+142A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3736+142A>G		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68836 AN: 151640 Hom.: 15977 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.418 AC: 148100 AN: 354432 Hom.: 32186 AF XY: 0.413 AC XY: 75793 AN XY: 183544

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.454 AC: 68912 AN: 151758 Hom.: 15998 Cov.: 30 AF XY: 0.453 AC XY: 33584 AN XY: 74158

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.459

Alfa AF: 0.444 Hom.: 2476

Bravo AF: 0.469

Asia WGS AF: 0.386 AC: 1343 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	-0.97
CADD	Benign	1.8
DANN	Benign	0.71

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: rs7652191; hg19: chr3-52610415; COSMIC: COSV56299339;