3-52603423-T-C

Position:

• chr3-52603423-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000707071.1(PBRM1):​c.2824+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,274,732 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (400 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (260 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.827

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-52603423-T-C is Benign according to our data. Variant chr3-52603423-T-C is described in ClinVar as [Benign]. Clinvar id is 1274069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.2824+98A>G		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3001+98A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.2824+98A>G		intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6023 AN: 152216 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00407 AC: 4566 AN: 1122398 Hom.: 260 AF XY: 0.00378 AC XY: 2121 AN XY: 561834

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.000927

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.000298

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000529

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0396 AC: 6033 AN: 152334 Hom.: 400 Cov.: 32 AF XY: 0.0379 AC XY: 2823 AN XY: 74494

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0380 Hom.: 44

Bravo AF: 0.0455

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.54

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: rs17052322; hg19: chr3-52637439;