rs1047406

Positions:

• chr8-22713422-T-A
• chr8-22713422-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144962.3(PEBP4):​c.632A>T​(p.Glu211Val) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E211G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEBP4 NM_144962.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

Genes affected

PEBP4 (HGNC:28319): (phosphatidylethanolamine binding protein 4) The phosphatidylethanolamine (PE)-binding proteins, including PEBP4, are an evolutionarily conserved family of proteins with pivotal biologic functions, such as lipid binding and inhibition of serine proteases (Wang et al., 2004 [PubMed 15302887]).[supplied by OMIM, Dec 2008]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03781864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.632A>T	p.Glu211Val	missense_variant	7/7	ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.632A>T	p.Glu211Val	missense_variant	7/7		NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.632A>T	p.Glu211Val	missense_variant	7/7	1	NM_144962.3	ENSP00000256404	P1
	ENST00000523627.1	n.164+23109T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.078
DANN	Benign	0.75
DEOGEN2	Benign	0.00033	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.11
Sift	Benign	0.33	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.25		Gain of helix (P = 0.0078);
MVP		0.048
MPC		0.017
ClinPred		0.13	T
GERP RS		-8.3
Varity_R		0.052
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047406; hg19: chr8-22570935;