rs11574452

Positions:

• chr4-73980944-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002619.4(PF4):​c.*260G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 461,744 control chromosomes in the GnomAD database, including 840 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 0.046 (239 hom., cov: 33)
  • Exomes 𝑓: 0.052 (601 hom.)
• Consequence: PF4 NM_002619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

Genes affected

PF4 (HGNC:8861): (platelet factor 4) This gene encodes a member of the CXC chemokine family. This chemokine is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell type and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. The protein also exhibits antimicrobial activity against Plasmodium falciparum. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PF4	NM_002619.4	c.*260G>T		3_prime_UTR_variant	3/3	ENST00000296029.4	NP_002610.1
PF4	NM_001363352.1	c.*260G>T		3_prime_UTR_variant	3/3		NP_001350281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PF4	ENST00000296029.4	c.*260G>T		3_prime_UTR_variant	3/3	1	NM_002619.4	ENSP00000296029	P1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6963 AN: 152194 Hom.: 238 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0525

GnomAD4 exome AF: 0.0517 AC: 16006 AN: 309432 Hom.: 601 AF XY: 0.0521 AC XY: 8454 AN XY: 162168

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0743

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.0502

Gnomad4 FIN exome AF: 0.0343

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.0457 AC: 6958 AN: 152312 Hom.: 239 Cov.: 33 AF XY: 0.0472 AC XY: 3512 AN XY: 74468

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0430

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0509 Hom.: 358

Bravo AF: 0.0534

Asia WGS AF: 0.0990 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11574452; hg19: chr4-74846661;