rs2457426

Positions:

• chr8-22928637-A-C
• chr8-22928637-A-T

Variant summary

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

The NM_001363233.2(PEBP4):​c.-6-917T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,710 control chromosomes in the GnomAD database, including 12,772 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 0.40 (12772 hom., cov: 30)
• Consequence: PEBP4 NM_001363233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_001363233.2	c.-6-917T>G		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000522278.1	c.145-917T>G		intron_variant		5		ENSP00000429414
PEBP4	ENST00000521284.1	n.66-917T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60192 AN: 151590 Hom.: 12766 Cov.: 30

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.397 AC: 60224 AN: 151710 Hom.: 12772 Cov.: 30 AF XY: 0.395 AC XY: 29293 AN XY: 74104

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.411

Alfa AF: 0.437 Hom.: 12167

Bravo AF: 0.385

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2457426; hg19: chr8-22786150;