rs2251219

Variant names:

• chr3-52550771-T-A
• rs2251219
• NM_001405607.1:c.4701A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52550771-T-A
• chr3-52550771-T-C
• chr3-52550771-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001405607.1(PBRM1):​c.4701A>T​(p.Pro1567Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PBRM1 NM_001405607.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 117 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.4701A>T	p.Pro1567Pro	synonymous	Exon 30 of 32	NP_001392536.1	A0A9L9PXL4
	PBRM1	NM_001405601.1		c.4701A>T	p.Pro1567Pro	synonymous	Exon 30 of 32	NP_001392530.1	A0A9L9PXL4
	PBRM1	NM_001405598.1		c.4683A>T	p.Pro1561Pro	synonymous	Exon 29 of 31	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.4701A>T	p.Pro1567Pro	synonymous	Exon 30 of 32	ENSP00000516722.1	A0A9L9PXL4
	PBRM1	ENST00000296302.11	TSL:1	c.4656A>T	p.Pro1552Pro	synonymous	Exon 28 of 30	ENSP00000296302.7	Q86U86-1
	PBRM1	ENST00000409114.7	TSL:1	c.4545A>T	p.Pro1515Pro	synonymous	Exon 28 of 30	ENSP00000386643.3	Q86U86-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Other links and lift over

dbSNP: rs2251219; hg19: chr3-52584787;