8-22779707-C-T

Variant summary

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

The NM_144962.3(PEBP4):c.357+37930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,094 control chromosomes in the GnomAD database, including 17,693 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 0.46 (17693 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEBP4	NM_144962.3	c.357+37930G>A		intron_variant		ENST00000256404.8
PEBP4	NM_001363233.2	c.357+37930G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEBP4	ENST00000256404.8	c.357+37930G>A		intron_variant		1	NM_144962.3	P1
	ENST00000523627.1	n.490-18829C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70295 AN: 151976 Hom.: 17693 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.462 AC: 70327 AN: 152094 Hom.: 17693 Cov.: 32 AF XY: 0.462 AC XY: 34347 AN XY: 74340

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.489

Alfa AF: 0.544 Hom.: 25009

Bravo AF: 0.457

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.78
Dann	Benign	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: rs2055822; hg19: chr8-22637220;