dbSNP rs547790173: PBRM1:p.Asn333Ser (chr3-52642043-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The ENST00000707071.1(PBRM1):c.998A>G(p.Asn333Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,513,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

PBRM1
ENST00000707071.1 missense, splice_region

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.36

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
PBRM1	NM_001405601.1 link	c.998A>G	p.Asn333Ser	missense_variant, splice_region_variant	Exon 11 of 32	NP_001392530.1
PBRM1	NM_001405607.1 link	c.998A>G	p.Asn333Ser	missense_variant, splice_region_variant	Exon 11 of 32	NP_001392536.1
PBRM1	NM_001405598.1 link	c.1025A>G	p.Asn342Ser	missense_variant, splice_region_variant	Exon 11 of 31	NP_001392527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1 link	c.998A>G	p.Asn333Ser	missense_variant, splice_region_variant	Exon 11 of 32			ENSP00000516722.1		A0A9L9PXL4

Frequencies

GnomAD3 genomes

AF:

0.0000727

AC:

AN:

151394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000592

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000228

AC:

AN:

232166

AF XY:

0.000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000521

AC:

AN:

1361504

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

682292

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31418

American (AMR)

AF:

0.00168

AC:

AN:

41780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25302

East Asian (EAS)

AF:

0.00

AC:

AN:

39138

South Asian (SAS)

AF:

0.00

AC:

AN:

82666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026654

Other (OTH)

AF:

0.00

AC:

AN:

56880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000726

AC:

AN:

151512

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73992

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41338

American (AMR)

AF:

0.000591

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67872

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000148

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;.;T;.;.;.;.;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

T;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.046

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;L;L;L;L;L;L;.;.

PhyloP100

7.4

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.33

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T;T;T;.;.

Polyphen

0.99

D;D;B;D;D;D;D;D;.;.

Vest4

0.58

MVP

0.58

MPC

0.82

ClinPred

0.18

GERP RS

5.7

Varity_R

0.12

gMVP

0.33

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.53

Position offset: -1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over