chr12-118137291-T-C

Position:

• chr12-118137291-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.136-748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,912 control chromosomes in the GnomAD database, including 17,326 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 0.46 (17326 hom., cov: 31)
• Consequence: PEBP1 NM_002567.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP1	NM_002567.4	c.136-748T>C		intron_variant		ENST00000261313.3	NP_002558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP1	ENST00000261313.3	c.136-748T>C		intron_variant		1	NM_002567.4	ENSP00000261313.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70010 AN: 151794 Hom.: 17282 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.461 AC: 70102 AN: 151912 Hom.: 17326 Cov.: 31 AF XY: 0.463 AC XY: 34391 AN XY: 74248

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.471

Alfa AF: 0.383 Hom.: 15303

Bravo AF: 0.468

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
DANN	Benign	0.42

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: rs2088702; hg19: chr12-118575096;