rs2293444

Variant names:

• chr12-118136377-A-C
• rs2293444
• NM_002567.4:c.135+33A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-118136377-A-C
• chr12-118136377-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.81).
• 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 rank	MANE	Protein	UniProt
PEBP1	NM_002567.4	c.135+33A>C		intron_variant	Intron 1 of 3	ENST00000261313.3	NP_002558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEBP1	ENST00000261313.3	c.135+33A>C		intron_variant	Intron 1 of 3	1	NM_002567.4	ENSP00000261313.2

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

GnomAD2 exomes AF: 0.198 AC: 24395 AN: 123016 AF XY: 0.196

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 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

African (AFR) AF: 0.319 AC: 9848 AN: 30850

American (AMR) AF: 0.228 AC: 7947 AN: 34894

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3756 AN: 24404

East Asian (EAS) AF: 0.558 AC: 19726 AN: 35336

South Asian (SAS) AF: 0.248 AC: 19184 AN: 77212

European-Finnish (FIN) AF: 0.107 AC: 3948 AN: 36986

Middle Eastern (MID) AF: 0.215 AC: 885 AN: 4108

European-Non Finnish (NFE) AF: 0.0942 AC: 101199 AN: 1073916

Other (OTH) AF: 0.158 AC: 9072 AN: 57240

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

African (AFR) AF: 0.310 AC: 12842 AN: 41478

American (AMR) AF: 0.216 AC: 3296 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2727 AN: 5082

South Asian (SAS) AF: 0.274 AC: 1324 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1108 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6809 AN: 67960

Other (OTH) AF: 0.187 AC: 395 AN: 2114

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
PhyloP100		-1.6
PromoterAI		0.13	Neutral
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: rs2293444; hg19: chr12-118574182;