8-22713422-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144962.3(PEBP4):ā€‹c.632A>Gā€‹(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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.31 ( 7339 hom., cov: 33)
Exomes š‘“: 0.31 ( 72469 hom. )

Consequence

PEBP4
NM_144962.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.40
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEBP4NM_144962.3 linkuse as main transcriptc.632A>G p.Glu211Gly missense_variant 7/7 ENST00000256404.8 NP_659399.2
PEBP4NM_001363233.2 linkuse as main transcriptc.632A>G p.Glu211Gly missense_variant 7/7 NP_001350162.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEBP4ENST00000256404.8 linkuse as main transcriptc.632A>G p.Glu211Gly missense_variant 7/71 NM_144962.3 ENSP00000256404 P1
ENST00000523627.1 linkuse as main transcriptn.164+23109T>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.306
AC:
46527
AN:
151968
Hom.:
7329
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.316
AC:
77811
AN:
246620
Hom.:
13010
AF XY:
0.306
AC XY:
40925
AN XY:
133894
show subpopulations
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 SAS exome
AF:
0.209
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
show subpopulations
Gnomad4 AFR exome
AF:
0.253
Gnomad4 AMR exome
AF:
0.446
Gnomad4 ASJ exome
AF:
0.369
Gnomad4 EAS exome
AF:
0.314
Gnomad4 SAS exome
AF:
0.213
Gnomad4 FIN exome
AF:
0.307
Gnomad4 NFE exome
AF:
0.316
Gnomad4 OTH exome
AF:
0.306
GnomAD4 genome
AF:
0.306
AC:
46573
AN:
152086
Hom.:
7339
Cov.:
33
AF XY:
0.308
AC XY:
22902
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.257
Gnomad4 AMR
AF:
0.415
Gnomad4 ASJ
AF:
0.362
Gnomad4 EAS
AF:
0.313
Gnomad4 SAS
AF:
0.211
Gnomad4 FIN
AF:
0.307
Gnomad4 NFE
AF:
0.314
Gnomad4 OTH
AF:
0.311
Alfa
AF:
0.316
Hom.:
18967
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 v4.3

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
MutationTaster
Benign
1.0
P
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1047406; hg19: chr8-22570935; COSMIC: COSV56463462; API