ENST00000707071.1:c.4725+48T>C

Variant names:

• chr3-52550699-A-G
• rs2878628
• ENST00000707071.1:c.4725+48T>C

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.4725+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,582,072 control chromosomes in the GnomAD database, including 135,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13402 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122191 hom.)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279
• Publications: 28 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=-0.76).
• BP6: Variant 3-52550699-A-G is Benign according to our data. Variant chr3-52550699-A-G is described in ClinVar as [Benign]. Clinvar id is 1178095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBRM1	NM_001405601.1	c.4725+48T>C		intron_variant	Intron 30 of 31		NP_001392530.1
PBRM1	NM_001405607.1	c.4725+48T>C		intron_variant	Intron 30 of 31		NP_001392536.1
PBRM1	NM_001405598.1	c.4707+48T>C		intron_variant	Intron 29 of 30		NP_001392527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.4725+48T>C		intron_variant	Intron 30 of 31			ENSP00000516722.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63198 AN: 151970 Hom.: 13388 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.419 AC: 102049 AN: 243404 AF XY: 0.408

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.425

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.410 AC: 586301 AN: 1429984 Hom.: 122191 Cov.: 23 AF XY: 0.405 AC XY: 288921 AN XY: 712700

African (AFR) AF: 0.394 AC: 12903 AN: 32726

American (AMR) AF: 0.537 AC: 23031 AN: 42866

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11990 AN: 25322

East Asian (EAS) AF: 0.477 AC: 18809 AN: 39406

South Asian (SAS) AF: 0.276 AC: 23343 AN: 84720

European-Finnish (FIN) AF: 0.408 AC: 21690 AN: 53162

Middle Eastern (MID) AF: 0.441 AC: 2508 AN: 5686

European-Non Finnish (NFE) AF: 0.412 AC: 448255 AN: 1086826

Other (OTH) AF: 0.401 AC: 23772 AN: 59270

GnomAD4 genome AF: 0.416 AC: 63264 AN: 152088 Hom.: 13402 Cov.: 32 AF XY: 0.416 AC XY: 30953 AN XY: 74344

African (AFR) AF: 0.387 AC: 16038 AN: 41468

American (AMR) AF: 0.504 AC: 7695 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2216 AN: 5166

South Asian (SAS) AF: 0.279 AC: 1348 AN: 4830

European-Finnish (FIN) AF: 0.398 AC: 4212 AN: 10586

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28674 AN: 67980

Other (OTH) AF: 0.431 AC: 911 AN: 2114

Alfa AF: 0.433 Hom.: 3710

Bravo AF: 0.425

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		-0.28
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: rs2878628; hg19: chr3-52584715; COSMIC: COSV56259373; COSMIC: COSV56259373;