rs1051470

Variant names:

• chr12-118145427-T-C
• rs1051470
• NM_002567.4:c.*624T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002567.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP1	NM_002567.4	MANE Select	c.*624T>C		3_prime_UTR	Exon 4 of 4	NP_002558.1	P30086

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP1	ENST00000261313.3	TSL:1 MANE Select	c.*624T>C		3_prime_UTR	Exon 4 of 4	ENSP00000261313.2	P30086
	PEBP1	ENST00000874099.1		c.*624T>C		3_prime_UTR	Exon 4 of 4	ENSP00000544158.1
	PEBP1	ENST00000874100.1		c.*624T>C		3_prime_UTR	Exon 4 of 4	ENSP00000544159.1

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

African (AFR) AF: 0.778 AC: 14 AN: 18

American (AMR) AF: 0.679 AC: 1183 AN: 1742

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 20 AN: 42

East Asian (EAS) AF: 0.579 AC: 175 AN: 302

South Asian (SAS) AF: 0.719 AC: 798 AN: 1110

European-Finnish (FIN) AF: 0.585 AC: 96 AN: 164

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.586 AC: 3233 AN: 5520

Other (OTH) AF: 0.606 AC: 223 AN: 368

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

African (AFR) AF: 0.726 AC: 30080 AN: 41450

American (AMR) AF: 0.679 AC: 10362 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3581 AN: 5150

South Asian (SAS) AF: 0.746 AC: 3596 AN: 4818

European-Finnish (FIN) AF: 0.609 AC: 6431 AN: 10554

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41199 AN: 67960

Other (OTH) AF: 0.617 AC: 1304 AN: 2112

Alfa AF: 0.638 Hom.: 7469

Bravo AF: 0.660

Asia WGS AF: 0.691 AC: 2403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.52
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051470; hg19: chr12-118583232;