chr3-52586698-G-T

Position:

• chr3-52586698-G-T

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.3169-10C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,559,158 control chromosomes in the GnomAD database, including 1,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (542 hom., cov: 28)
  • Exomes 𝑓: 0.0064 (543 hom.)
• Consequence: PBRM1 ENST00000707071.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006627
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.202

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=-0.84).
• BP6: Variant 3-52586698-G-T is Benign according to our data. Variant chr3-52586698-G-T is described in ClinVar as [Benign]. Clinvar id is 1221074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBRM1	NM_001405607.1	c.3169-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000707071.1
PBRM1	NR_175959.1	n.3346-10C>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBRM1	ENST00000707071.1	c.3169-10C>A		splice_polypyrimidine_tract_variant, intron_variant			NM_001405607.1	A1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 6768 AN: 143116 Hom.: 540 Cov.: 28

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00887

Gnomad FIN AF: 0.000124

Gnomad MID AF: 0.0207

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0393

GnomAD3 exomes AF: 0.0134 AC: 3248 AN: 241972 Hom.: 241 AF XY: 0.0103 AC XY: 1359 AN XY: 131984

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.00710

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.00566

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.00190

Gnomad OTH exome AF: 0.00738

GnomAD4 exome AF: 0.00637 AC: 9023 AN: 1415944 Hom.: 543 Cov.: 25 AF XY: 0.00576 AC XY: 4053 AN XY: 703932

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.00913

Gnomad4 ASJ exome AF: 0.0000802

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.00568

Gnomad4 FIN exome AF: 0.0000388

Gnomad4 NFE exome AF: 0.00162

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.0474 AC: 6790 AN: 143214 Hom.: 542 Cov.: 28 AF XY: 0.0468 AC XY: 3222 AN XY: 68824

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00868

Gnomad4 FIN AF: 0.000124

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.0394

Alfa AF: 0.0364 Hom.: 92

Bravo AF: 0.0558

Asia WGS AF: 0.0150 AC: 52 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 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.032
SpliceAI score (max)		0.030		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: rs72947594; hg19: chr3-52620714; COSMIC: COSV56274082;