rs2466215

Positions:

• chr8-22917906-A-G

Variant summary

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

The NM_144962.3(PEBP4):​c.258+2278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,174 control chromosomes in the GnomAD database, including 2,130 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 0.15 (2130 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEBP4	NM_144962.3	c.258+2278T>C		intron_variant		ENST00000256404.8
PEBP4	NM_001363233.2	c.258+2278T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEBP4	ENST00000256404.8	c.258+2278T>C		intron_variant		1	NM_144962.3	P1
PEBP4	ENST00000521284.1	n.329+2278T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23198 AN: 152056 Hom.: 2129 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.153 AC: 23210 AN: 152174 Hom.: 2130 Cov.: 32 AF XY: 0.147 AC XY: 10971 AN XY: 74396

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.157

Alfa AF: 0.192 Hom.: 1674

Bravo AF: 0.149

Asia WGS AF: 0.0660 AC: 230 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	0.082
DANN	Benign	0.81

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: rs2466215; hg19: chr8-22775419;