rs2293444

chr12-118136377-A-Cchr12-118136377-A-G

Variant summary

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

The NM_002567.4(PEBP1):c.135+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,526,952 control chromosomes in the GnomAD database, including 20,903 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 0.19 (3764 hom., cov: 32)
  • Exomes 𝑓: 0.13 (17139 hom.)
• Consequence: PEBP1 NM_002567.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

PEBP1 (HGNC:8630): (phosphatidylethanolamine binding protein 1) This gene encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways, including the MAP kinase (MAPK), NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways. The encoded protein can be further processed to form a smaller cleavage product, hippocampal cholinergic neurostimulating peptide (HCNP), which may be involved in neural development. This gene has been implicated in numerous human cancers and may act as a metastasis suppressor gene. Multiple pseudogenes of this gene have been identified in the genome. [provided by RefSeq, Jul 2015]

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 (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEBP1	NM_002567.4	c.135+33A>C		intron_variant		ENST00000261313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEBP1	ENST00000261313.3	c.135+33A>C		intron_variant		1	NM_002567.4	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29165 AN: 151886 Hom.: 3759 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.198 AC: 24395 AN: 123016 Hom.: 3341 AF XY: 0.196 AC XY: 13090 AN XY: 66952

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.504

Gnomad SAS exome AF: 0.244

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.128 AC: 175565 AN: 1374946 Hom.: 17139 Cov.: 32 AF XY: 0.131 AC XY: 88677 AN XY: 677662

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0942

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.192 AC: 29192 AN: 152006 Hom.: 3764 Cov.: 32 AF XY: 0.196 AC XY: 14550 AN XY: 74310

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.187

Alfa AF: 0.142 Hom.: 387

Bravo AF: 0.204

Asia WGS AF: 0.372 AC: 1291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.1
Dann	Benign	0.38

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: rs2293444; hg19: chr12-118574182;