8-22713422-T-C

Variant names:

• chr8-22713422-T-C
• rs1047406
• NM_144962.3:c.632A>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.632A>G​(p.Glu211Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,610,552 control chromosomes in the GnomAD database, including 79,808 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7339 hom., cov: 33)
  • Exomes 𝑓: 0.31 (72469 hom.)
• Consequence: PEBP4 NM_144962.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• Publications: 24 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]

EGR3-AS1 (HGNC:58186):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.9481778E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	NM_144962.3	MANE Select	c.632A>G	p.Glu211Gly	missense	Exon 7 of 7	NP_659399.2	Q96S96
	PEBP4	NM_001363233.2		c.632A>G	p.Glu211Gly	missense	Exon 7 of 7	NP_001350162.1	Q96S96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	ENST00000256404.8	TSL:1 MANE Select	c.632A>G	p.Glu211Gly	missense	Exon 7 of 7	ENSP00000256404.6	Q96S96
	PEBP4	ENST00000901323.1		c.662A>G	p.Glu221Gly	missense	Exon 8 of 8	ENSP00000571382.1
	PEBP4	ENST00000901324.1		c.632A>G	p.Glu211Gly	missense	Exon 7 of 7	ENSP00000571383.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46527 AN: 151968 Hom.: 7329 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.309

GnomAD2 exomes AF: 0.316 AC: 77811 AN: 246620 AF XY: 0.306

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.447

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.313

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.312 AC: 455549 AN: 1458466 Hom.: 72469 Cov.: 36 AF XY: 0.309 AC XY: 224125 AN XY: 725562

African (AFR) AF: 0.253 AC: 8408 AN: 33268

American (AMR) AF: 0.446 AC: 19604 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 9565 AN: 25940

East Asian (EAS) AF: 0.314 AC: 12458 AN: 39644

South Asian (SAS) AF: 0.213 AC: 18330 AN: 85998

European-Finnish (FIN) AF: 0.307 AC: 16386 AN: 53324

Middle Eastern (MID) AF: 0.281 AC: 1530 AN: 5436

European-Non Finnish (NFE) AF: 0.316 AC: 350870 AN: 1110670

Other (OTH) AF: 0.306 AC: 18398 AN: 60192

GnomAD4 genome AF: 0.306 AC: 46573 AN: 152086 Hom.: 7339 Cov.: 33 AF XY: 0.308 AC XY: 22902 AN XY: 74352

African (AFR) AF: 0.257 AC: 10682 AN: 41500

American (AMR) AF: 0.415 AC: 6346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1616 AN: 5166

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3240 AN: 10566

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21340 AN: 67960

Other (OTH) AF: 0.311 AC: 658 AN: 2114

Alfa AF: 0.315 Hom.: 25176

Bravo AF: 0.312

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.322 AC: 1242

ESP6500AA AF: 0.265 AC: 1044

ESP6500EA AF: 0.315 AC: 2614

ExAC AF: 0.308 AC: 37261

Asia WGS AF: 0.280 AC: 975 AN: 3478

EpiCase AF: 0.317

EpiControl AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.031
DANN	Benign	0.34
DEOGEN2	Benign	0.000085	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.00019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-3.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.082
Sift	Benign	0.73	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.017
ClinPred		0.0011	T
GERP RS		-8.3
Varity_R		0.022
gMVP		0.30
Mutation Taster		=99/1	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: rs1047406; hg19: chr8-22570935; COSMIC: COSV56463462;