rs1051470

chr12-118145427-T-C

Variant summary

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

The NM_002567.4(PEBP1):c.*624T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 161,264 control chromosomes in the GnomAD database, including 34,724 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 0.65 (32887 hom., cov: 31)
  • Exomes 𝑓: 0.62 (1837 hom.)
• Consequence: PEBP1 NM_002567.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEBP1	NM_002567.4	c.*624T>C		3_prime_UTR_variant	4/4	ENST00000261313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEBP1	ENST00000261313.3	c.*624T>C		3_prime_UTR_variant	4/4	1	NM_002567.4	P1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99318 AN: 151868 Hom.: 32843 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.619 AC: 5746 AN: 9278 Hom.: 1837 Cov.: 0 AF XY: 0.628 AC XY: 3168 AN XY: 5044

Gnomad4 AFR exome AF: 0.778

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.654 AC: 99418 AN: 151986 Hom.: 32887 Cov.: 31 AF XY: 0.656 AC XY: 48739 AN XY: 74274

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.617

Alfa AF: 0.636 Hom.: 7262

Bravo AF: 0.660

Asia WGS AF: 0.691 AC: 2403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.3
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1051470; hg19: chr12-118583232;