dbSNP rs11574452: PF4:c.*260G>T (chr4-73980944-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.118

Publications

11 publications found

Variant links:

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]

PF4 links:

ENSG00000288796 (HGNC:):

ENSG00000288796 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PF4	NM_002619.4 link	c.*260G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000296029.4	NP_002610.1	P02776
PF4	NM_001363352.1 link	c.*260G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001350281.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PF4	ENST00000296029.4 link	c.*260G>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_002619.4	ENSP00000296029.3	P02776
ENSG00000288796	ENST00000693342.1 link	c.*260G>T	downstream_gene_variant				ENSP00000510492.1	A0A8I5KW61
PF4	ENST00000687529.1 link	n.*597G>T	downstream_gene_variant				ENSP00000508485.1	A0A8I5QJ57
ENSG00000288796	ENST00000689521.1 link	n.*958G>T	downstream_gene_variant				ENSP00000509524.1	A0A8I5KUZ5

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6963

AN:

152194

Hom.:

238

Cov.:

show subpopulations

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

show subpopulations

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:

AN:

1418

European-Non Finnish (NFE)

AF:

0.0411

AC:

7804

AN:

189790

Other (OTH)

AF:

0.0577

AC:

1052

AN:

18238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

710

1420

2131

2841

3551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0457

AC:

6958

AN:

152312

Hom.:

239

Cov.:

AF XY:

0.0472

AC XY:

3512

AN XY:

74468

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0430

AC:

2927

AN:

68026

Other (OTH)

AF:

0.0520

AC:

110

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

334

668

1001

1335

1669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.58

PhyloP100

-0.12

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over