8-22790337-T-C

Position:

• chr8-22790337-T-C

Variant summary

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

The NM_144962.3(PEBP4):​c.357+27300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,994 control chromosomes in the GnomAD database, including 11,384 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 0.38 (11384 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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]

ENSG00000253125 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.357+27300A>G		intron_variant		ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.357+27300A>G		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.357+27300A>G		intron_variant		1	NM_144962.3	ENSP00000256404.6
ENSG00000253125	ENST00000523627.1	n.490-8199T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57977 AN: 151876 Hom.: 11376 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.404

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 58020 AN: 151994 Hom.: 11384 Cov.: 32 AF XY: 0.385 AC XY: 28568 AN XY: 74282

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.402

Alfa AF: 0.405 Hom.: 17755

Bravo AF: 0.386

Asia WGS AF: 0.354 AC: 1230 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.052
DANN	Benign	0.54

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: rs17088625; hg19: chr8-22647850;