ENST00000707071.1:c.4654+85C>T

Variant names:

• chr3-52554639-G-A
• rs2336142
• NM_001405607.1:c.4654+85C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000707071.1(PBRM1):​c.4654+85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 1,220,390 control chromosomes in the GnomAD database, including 5,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (478 hom., cov: 32)
  • Exomes 𝑓: 0.090 (4719 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-52554639-G-A is Benign according to our data. Variant chr3-52554639-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000707071.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.4654+85C>T		intron	N/A	NP_001392536.1	A0A9L9PXL4
	PBRM1	NM_001405601.1		c.4654+85C>T		intron	N/A	NP_001392530.1	A0A9L9PXL4
	PBRM1	NM_001405598.1		c.4636+85C>T		intron	N/A	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.4654+85C>T		intron	N/A	ENSP00000516722.1	A0A9L9PXL4
	PBRM1	ENST00000296302.11	TSL:1	c.4609+85C>T		intron	N/A	ENSP00000296302.7	Q86U86-1
	PBRM1	ENST00000409114.7	TSL:1	c.4498+3610C>T		intron	N/A	ENSP00000386643.3	Q86U86-8

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10552 AN: 152114 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0903 AC: 96443 AN: 1068158 Hom.: 4719 AF XY: 0.0910 AC XY: 48119 AN XY: 528492

African (AFR) AF: 0.0142 AC: 326 AN: 22928

American (AMR) AF: 0.0472 AC: 871 AN: 18438

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2056 AN: 17428

East Asian (EAS) AF: 0.000155 AC: 5 AN: 32236

South Asian (SAS) AF: 0.0863 AC: 4649 AN: 53900

European-Finnish (FIN) AF: 0.126 AC: 6040 AN: 47830

Middle Eastern (MID) AF: 0.110 AC: 502 AN: 4552

European-Non Finnish (NFE) AF: 0.0945 AC: 77964 AN: 824926

Other (OTH) AF: 0.0878 AC: 4030 AN: 45920

GnomAD4 genome AF: 0.0693 AC: 10548 AN: 152232 Hom.: 478 Cov.: 32 AF XY: 0.0711 AC XY: 5295 AN XY: 74428

African (AFR) AF: 0.0189 AC: 785 AN: 41542

American (AMR) AF: 0.0628 AC: 961 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 401 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1376 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6367 AN: 67996

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0871 Hom.: 1135

Bravo AF: 0.0625

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.62
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2336142; hg19: chr3-52588655;