rs10503717

Variant names:

• chr8-22721359-A-C
• rs10503717
• NM_144962.3:c.517+3484T>G

Variant summary

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

The NM_144962.3(PEBP4):​c.517+3484T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,978 control chromosomes in the GnomAD database, including 4,587 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 0.24 (4587 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 4 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]

ENSG00000253125 (HGNC:58186):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.517+3484T>G		intron_variant	Intron 6 of 6	ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.517+3484T>G		intron_variant	Intron 6 of 6		NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.517+3484T>G		intron_variant	Intron 6 of 6	1	NM_144962.3	ENSP00000256404.6
ENSG00000253125	ENST00000523627.1	n.165-23235A>C		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36574 AN: 151860 Hom.: 4583 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.241 AC: 36603 AN: 151978 Hom.: 4587 Cov.: 32 AF XY: 0.241 AC XY: 17904 AN XY: 74288

African (AFR) AF: 0.196 AC: 8109 AN: 41456

American (AMR) AF: 0.344 AC: 5252 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1166 AN: 5154

South Asian (SAS) AF: 0.195 AC: 936 AN: 4808

European-Finnish (FIN) AF: 0.236 AC: 2487 AN: 10560

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16641 AN: 67932

Other (OTH) AF: 0.249 AC: 526 AN: 2110

Alfa AF: 0.247 Hom.: 20408

Bravo AF: 0.248

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10503717; hg19: chr8-22578872;