rs2304717

Variant names:

• chr15-74034216-T-C
• rs2304717
• ENST00000563500.5:c.*608T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-74034216-T-C
• chr15-74034216-T-G

Variant summary

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

The ENST00000563500.5(PML):​c.*608T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 539,790 control chromosomes in the GnomAD database, including 75,824 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 0.50 (19735 hom., cov: 32)
  • Exomes 𝑓: 0.53 (56089 hom.)
• Consequence: PML ENST00000563500.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 5 publications found

Genes affected

PML (HGNC:9113): (PML nuclear body scaffold) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PML	NM_033238.3	c.1658-262T>C		intron_variant	Intron 6 of 8	ENST00000268058.8	NP_150241.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PML	ENST00000268058.8	c.1658-262T>C		intron_variant	Intron 6 of 8	1	NM_033238.3	ENSP00000268058.3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76602 AN: 151980 Hom.: 19738 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.533 AC: 206521 AN: 387692 Hom.: 56089 Cov.: 4 AF XY: 0.530 AC XY: 108464 AN XY: 204720

African (AFR) AF: 0.401 AC: 4573 AN: 11418

American (AMR) AF: 0.524 AC: 10197 AN: 19442

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 5661 AN: 12166

East Asian (EAS) AF: 0.467 AC: 11654 AN: 24930

South Asian (SAS) AF: 0.483 AC: 22068 AN: 45694

European-Finnish (FIN) AF: 0.604 AC: 13217 AN: 21878

Middle Eastern (MID) AF: 0.469 AC: 762 AN: 1626

European-Non Finnish (NFE) AF: 0.556 AC: 126992 AN: 228400

Other (OTH) AF: 0.515 AC: 11397 AN: 22138

GnomAD4 genome AF: 0.504 AC: 76636 AN: 152098 Hom.: 19735 Cov.: 32 AF XY: 0.505 AC XY: 37567 AN XY: 74384

African (AFR) AF: 0.393 AC: 16300 AN: 41466

American (AMR) AF: 0.524 AC: 7996 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2316 AN: 5174

South Asian (SAS) AF: 0.484 AC: 2338 AN: 4830

European-Finnish (FIN) AF: 0.597 AC: 6316 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38305 AN: 67996

Other (OTH) AF: 0.490 AC: 1033 AN: 2110

Alfa AF: 0.537 Hom.: 3514

Bravo AF: 0.491

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.53
PhyloP100		-0.59
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: rs2304717; hg19: chr15-74326557;