rs11998649

Positions:

• chr8-22762038-A-C
• chr8-22762038-A-T

Variant summary

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

The NM_144962.3(PEBP4):​c.358-34818T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 149,666 control chromosomes in the GnomAD database, including 39,524 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 0.72 (39524 hom., cov: 25)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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]

ENSG00000253125 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.358-34818T>G		intron_variant		ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.358-34818T>G		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.358-34818T>G		intron_variant		1	NM_144962.3	ENSP00000256404.6
ENSG00000253125	ENST00000523627.1	n.489+14468A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.717 AC: 107158 AN: 149550 Hom.: 39511 Cov.: 25

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.716 AC: 107206 AN: 149666 Hom.: 39524 Cov.: 25 AF XY: 0.716 AC XY: 52140 AN XY: 72850

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.747

Alfa AF: 0.691 Hom.: 2221

Bravo AF: 0.709

Asia WGS AF: 0.698 AC: 2423 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.61

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: rs11998649; hg19: chr8-22619551;