chr8-22905735-A-G

Variant names:

• chr8-22905735-A-G
• rs6557600
• NM_144962.3:c.258+14449T>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+14449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,146 control chromosomes in the GnomAD database, including 4,225 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 0.23 (4225 hom., cov: 32)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 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+14449T>C		intron	N/A	NP_659399.2
	PEBP4	NM_001363233.2		c.258+14449T>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+14449T>C		intron	N/A	ENSP00000256404.6
	PEBP4	ENST00000521284.1	TSL:3	n.329+14449T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35476 AN: 152028 Hom.: 4217 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.233 AC: 35493 AN: 152146 Hom.: 4225 Cov.: 32 AF XY: 0.230 AC XY: 17143 AN XY: 74380

African (AFR) AF: 0.275 AC: 11415 AN: 41500

American (AMR) AF: 0.191 AC: 2921 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1018 AN: 5182

South Asian (SAS) AF: 0.122 AC: 590 AN: 4818

European-Finnish (FIN) AF: 0.213 AC: 2257 AN: 10586

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15407 AN: 67984

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.226 Hom.: 15365

Bravo AF: 0.235

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.85
DANN	Benign	0.24
PhyloP100		-0.49
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: rs6557600; hg19: chr8-22763248;