8-22918203-T-G

Variant names:

• chr8-22918203-T-G
• rs2466216
• NM_144962.3:c.258+1981A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144962.3(PEBP4):​c.258+1981A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,244 control chromosomes in the GnomAD database, including 1,988 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 0.14 (1988 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 11 publications found

Genes affected

PEBP4 (HGNC:28319): (phosphatidylethanolamine binding protein 4) The phosphatidylethanolamine (PE)-binding proteins, including PEBP4, are an evolutionarily conserved family of proteins with pivotal biologic functions, such as lipid binding and inhibition of serine proteases (Wang et al., 2004 [PubMed 15302887]).[supplied by OMIM, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144962.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	NM_144962.3	MANE Select	c.258+1981A>C		intron	N/A	NP_659399.2
	PEBP4	NM_001363233.2		c.258+1981A>C		intron	N/A	NP_001350162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	ENST00000256404.8	TSL:1 MANE Select	c.258+1981A>C		intron	N/A	ENSP00000256404.6
	PEBP4	ENST00000521284.1	TSL:3	n.329+1981A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21491 AN: 152126 Hom.: 1989 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.141 AC: 21488 AN: 152244 Hom.: 1988 Cov.: 32 AF XY: 0.136 AC XY: 10136 AN XY: 74438

African (AFR) AF: 0.0402 AC: 1669 AN: 41556

American (AMR) AF: 0.126 AC: 1926 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.0766 AC: 397 AN: 5186

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4822

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10608

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14512 AN: 67996

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.180 Hom.: 3868

Bravo AF: 0.137

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		1.2
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: rs2466216; hg19: chr8-22775716;