rs10503722

Positions:

• chr8-22918342-G-A

Variant summary

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

The NM_144962.3(PEBP4):​c.258+1842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,168 control chromosomes in the GnomAD database, including 1,712 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 0.13 (1712 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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]

PEBP4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.258+1842C>T		intron_variant		ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.258+1842C>T		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.258+1842C>T		intron_variant		1	NM_144962.3	ENSP00000256404.6
PEBP4	ENST00000521284.1	n.329+1842C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19808 AN: 152050 Hom.: 1713 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.130 AC: 19808 AN: 152168 Hom.: 1712 Cov.: 32 AF XY: 0.125 AC XY: 9323 AN XY: 74400

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.135

Alfa AF: 0.152 Hom.: 352

Bravo AF: 0.125

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.64

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: rs10503722; hg19: chr8-22775855;