Variant rs587777964 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000707071.1(PBRM1):c.1544A>G(p.Asn515Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,547,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

PBRM1
ENST00000707071.1 missense, splice_region

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.560

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.067670375).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBRM1	NM_001405607.1 linkuse as main transcript	c.1544A>G	p.Asn515Ser	missense_variant, splice_region_variant	15/32	ENST00000707071.1	NP_001392536.1
PBRM1	NR_175959.1 linkuse as main transcript	n.1721A>G		splice_region_variant, non_coding_transcript_exon_variant	15/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1 linkuse as main transcript	c.1544A>G	p.Asn515Ser	missense_variant, splice_region_variant	15/32		NM_001405607.1	ENSP00000516722	A1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000932

AC:

AN:

1395468

Hom.:

Cov.:

AF XY:

0.00000871

AC XY:

AN XY:

688492

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000743

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000378

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;D;D;D;D;N;N

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.083

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.53

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.10

MutPred

0.25

Gain of phosphorylation at N515 (P = 0.0016);Gain of phosphorylation at N515 (P = 0.0016);.;

MVP

0.34

ClinPred

0.26

GERP RS

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over