rs1961958

chr3-52551974-A-Gchr3-52551974-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707071.1(PBRM1):c.4655-1157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,110 control chromosomes in the GnomAD database, including 9,808 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 0.34 (9808 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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]

RNU6-856P (HGNC:47819): (RNA, U6 small nuclear 856, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.4655-1157T>C		intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.4798+236T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.4655-1157T>C		intron_variant			NM_001405607.1	A1
RNU6-856P	ENST00000516959.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51635 AN: 151992 Hom.: 9801 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.363

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.340 AC: 51663 AN: 152110 Hom.: 9808 Cov.: 32 AF XY: 0.342 AC XY: 25415 AN XY: 74346

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.369

Alfa AF: 0.380 Hom.: 3155

Bravo AF: 0.340

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	12
Dann	Benign	0.87

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: rs1961958; hg19: chr3-52585990;