chr8-22721359-A-C

Position:

• chr8-22721359-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PEBP4	NM_144962.3	c.517+3484T>G		intron_variant		ENST00000256404.8	NP_659399.2
PEBP4	NM_001363233.2	c.517+3484T>G		intron_variant			NP_001350162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEBP4	ENST00000256404.8	c.517+3484T>G		intron_variant		1	NM_144962.3	ENSP00000256404	P1
	ENST00000523627.1	n.165-23235A>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.249

Alfa AF: 0.251 Hom.: 10098

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503717; hg19: chr8-22578872;