rs11574452

Variant names:

• chr4-73980944-C-A
• rs11574452
• NM_002619.4:c.*260G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000288796 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002619.4. 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
	PF4	NM_002619.4	MANE Select	c.*260G>T		3_prime_UTR	Exon 3 of 3	NP_002610.1	P02776
	PF4	NM_001363352.1		c.*260G>T		3_prime_UTR	Exon 3 of 3	NP_001350281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PF4	ENST00000296029.4	TSL:1 MANE Select	c.*260G>T		3_prime_UTR	Exon 3 of 3	ENSP00000296029.3	P02776
	ENSG00000288796	ENST00000693342.1		c.*260G>T		downstream_gene	N/A	ENSP00000510492.1	A0A8I5KW61
	PF4	ENST00000687529.1		n.*597G>T		downstream_gene	N/A	ENSP00000508485.1	A0A8I5QJ57

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

African (AFR) AF: 0.0173 AC: 169 AN: 9782

American (AMR) AF: 0.121 AC: 1494 AN: 12300

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 742 AN: 9980

East Asian (EAS) AF: 0.125 AC: 2529 AN: 20278

South Asian (SAS) AF: 0.0502 AC: 1584 AN: 31574

European-Finnish (FIN) AF: 0.0343 AC: 552 AN: 16072

Middle Eastern (MID) AF: 0.0564 AC: 80 AN: 1418

European-Non Finnish (NFE) AF: 0.0411 AC: 7804 AN: 189790

Other (OTH) AF: 0.0577 AC: 1052 AN: 18238

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

African (AFR) AF: 0.0187 AC: 777 AN: 41566

American (AMR) AF: 0.0936 AC: 1433 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 274 AN: 3472

East Asian (EAS) AF: 0.135 AC: 700 AN: 5186

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4824

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0430 AC: 2927 AN: 68026

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0505 Hom.: 483

Bravo AF: 0.0534

Asia WGS AF: 0.0990 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs11574452; hg19: chr4-74846661;