dbSNP rs1961958: PBRM1:c.4655-1157T>C (chr3-52551974-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001405607.1(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
NM_001405607.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

24 publications found

Variant links:

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]

PBRM1 links:

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]

UQCC5 links:

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

RNU6-856P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405607.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PBRM1	NM_001405607.1	MANE Select	c.4655-1157T>C	intron	N/A	NP_001392536.1
PBRM1	NM_001405601.1		c.4655-1157T>C	intron	N/A	NP_001392530.1
PBRM1	NM_001405598.1		c.4637-1157T>C	intron	N/A	NP_001392527.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PBRM1	ENST00000707071.1	MANE Select	c.4655-1157T>C	intron	N/A	ENSP00000516722.1
PBRM1	ENST00000296302.11	TSL:1	c.4610-1157T>C	intron	N/A	ENSP00000296302.7
PBRM1	ENST00000409114.7	TSL:1	c.4499-1157T>C	intron	N/A	ENSP00000386643.3

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51635

AN:

151992

Hom.:

9801

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.340

AC:

51663

AN:

152110

Hom.:

9808

Cov.:

AF XY:

0.342

AC XY:

25415

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.176

AC:

7321

AN:

41528

American (AMR)

AF:

0.465

AC:

7098

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1558

AN:

3470

East Asian (EAS)

AF:

0.438

AC:

2263

AN:

5168

South Asian (SAS)

AF:

0.217

AC:

1048

AN:

4826

European-Finnish (FIN)

AF:

0.391

AC:

4128

AN:

10562

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.396

AC:

26926

AN:

67972

Other (OTH)

AF:

0.369

AC:

779

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1655

3311

4966

6622

8277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-0.085

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over