chr8-22853199-G-T

Position:

• chr8-22853199-G-T

Variant summary

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

The NM_144962.3(PEBP4):​c.259-35464C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,000 control chromosomes in the GnomAD database, including 18,554 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 0.49 (18554 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.259-35464C>A		intron_variant		ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.259-35464C>A		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.259-35464C>A		intron_variant		1	NM_144962.3	ENSP00000256404	P1
PEBP4	ENST00000521284.1	n.330-35464C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74822 AN: 151882 Hom.: 18536 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.493 AC: 74901 AN: 152000 Hom.: 18554 Cov.: 32 AF XY: 0.499 AC XY: 37049 AN XY: 74306

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.483

Alfa AF: 0.491 Hom.: 2291

Bravo AF: 0.485

Asia WGS AF: 0.648 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	16
DANN	Benign	0.71

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: rs2055824; hg19: chr8-22710712;