rs1987234

Variant names:

• chr3-52564343-T-C
• rs1987234
• NM_001405607.1:c.3737-110A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001405607.1(PBRM1):​c.3737-110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 820,578 control chromosomes in the GnomAD database, including 1,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (958 hom., cov: 31)
  • Exomes 𝑓: 0.025 (608 hom.)
• Consequence: PBRM1 NM_001405607.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.900
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-52564343-T-C is Benign according to our data. Variant chr3-52564343-T-C is described in ClinVar as Benign. ClinVar VariationId is 1282950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	NM_001405607.1	MANE Select	c.3737-110A>G		intron	N/A	NP_001392536.1	A0A9L9PXL4
	PBRM1	NM_001405601.1		c.3737-110A>G		intron	N/A	NP_001392530.1	A0A9L9PXL4
	PBRM1	NM_001405598.1		c.3719-110A>G		intron	N/A	NP_001392527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBRM1	ENST00000707071.1	MANE Select	c.3737-110A>G		intron	N/A	ENSP00000516722.1	A0A9L9PXL4
	PBRM1	ENST00000296302.11	TSL:1	c.3692-110A>G		intron	N/A	ENSP00000296302.7	Q86U86-1
	PBRM1	ENST00000409114.7	TSL:1	c.3737-110A>G		intron	N/A	ENSP00000386643.3	Q86U86-8

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11015 AN: 152100 Hom.: 952 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.0250 AC: 16726 AN: 668360 Hom.: 608 AF XY: 0.0248 AC XY: 8742 AN XY: 352248

African (AFR) AF: 0.224 AC: 3605 AN: 16086

American (AMR) AF: 0.0268 AC: 637 AN: 23752

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 285 AN: 19402

East Asian (EAS) AF: 0.000186 AC: 6 AN: 32254

South Asian (SAS) AF: 0.0366 AC: 2145 AN: 58564

European-Finnish (FIN) AF: 0.00590 AC: 232 AN: 39302

Middle Eastern (MID) AF: 0.0323 AC: 97 AN: 3002

European-Non Finnish (NFE) AF: 0.0194 AC: 8601 AN: 442504

Other (OTH) AF: 0.0334 AC: 1118 AN: 33494

GnomAD4 genome AF: 0.0726 AC: 11052 AN: 152218 Hom.: 958 Cov.: 31 AF XY: 0.0709 AC XY: 5276 AN XY: 74424

African (AFR) AF: 0.208 AC: 8617 AN: 41496

American (AMR) AF: 0.0404 AC: 618 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0382 AC: 184 AN: 4818

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1383 AN: 68028

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0531 Hom.: 86

Bravo AF: 0.0824

Asia WGS AF: 0.0280 AC: 100 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs1987234; hg19: chr3-52598359;