3-52684264-G-T

Variant names:

• chr3-52684264-G-T
• rs10865974
• ENST00000707071.1:c.-16+1485C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707071.1(PBRM1):​c.-16+1485C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 150,670 control chromosomes in the GnomAD database, including 16,076 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 0.46 (16076 hom., cov: 29)
• Consequence: PBRM1 ENST00000707071.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 26 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]

GNL3 (HGNC:29931): (G protein nucleolar 3) The protein encoded by this gene may interact with p53 and may be involved in tumorigenesis. The encoded protein also appears to be important for stem cell proliferation. This protein is found in both the nucleus and nucleolus. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBRM1	XM_047448442.1	c.-2251C>A		5_prime_UTR_variant	Exon 2 of 34		XP_047304398.1
PBRM1	XM_047448443.1	c.-2251C>A		5_prime_UTR_variant	Exon 2 of 34		XP_047304399.1
PBRM1	XM_047448444.1	c.-2251C>A		5_prime_UTR_variant	Exon 2 of 34		XP_047304400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBRM1	ENST00000707071.1	c.-16+1485C>A		intron_variant	Intron 1 of 31			ENSP00000516722.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 68964 AN: 150562 Hom.: 16056 Cov.: 29

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69040 AN: 150670 Hom.: 16076 Cov.: 29 AF XY: 0.458 AC XY: 33651 AN XY: 73522

African (AFR) AF: 0.526 AC: 21545 AN: 40998

American (AMR) AF: 0.524 AC: 7954 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1616 AN: 3460

East Asian (EAS) AF: 0.432 AC: 2216 AN: 5128

South Asian (SAS) AF: 0.273 AC: 1295 AN: 4742

European-Finnish (FIN) AF: 0.409 AC: 4155 AN: 10158

Middle Eastern (MID) AF: 0.503 AC: 144 AN: 286

European-Non Finnish (NFE) AF: 0.424 AC: 28736 AN: 67752

Other (OTH) AF: 0.463 AC: 963 AN: 2078

Alfa AF: 0.468 Hom.: 8945

Bravo AF: 0.470

Asia WGS AF: 0.379 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.34
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10865974; hg19: chr3-52718280;