rs367951530

Variant names:

• chr4-73981468-G-A
• rs367951530
• NM_002619.4:c.167C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-73981468-G-A
• chr4-73981468-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002619.4(PF4):​c.167C>T​(p.Thr56Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PF4 NM_002619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0801774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PF4	NM_002619.4	c.167C>T	p.Thr56Ile	missense_variant	Exon 2 of 3	ENST00000296029.4	NP_002610.1
PF4	NM_001363352.1	c.194C>T	p.Thr65Ile	missense_variant	Exon 2 of 3		NP_001350281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PF4	ENST00000296029.4	c.167C>T	p.Thr56Ile	missense_variant	Exon 2 of 3	1	NM_002619.4	ENSP00000296029.3
ENSG00000288796	ENST00000693342.1	c.443C>T	p.Thr148Ile	missense_variant	Exon 4 of 5			ENSP00000510492.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.85	L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.010
Sift	Benign	0.22	T
Sift4G	Benign	0.098	T
Polyphen		0.094	B
Vest4		0.14
MutPred		0.35		Loss of disorder (P = 0.0795);
MVP		0.23
MPC		0.11
ClinPred		0.12	T
GERP RS		-3.9
Varity_R		0.17
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs367951530; hg19: chr4-74847185;