rs12063091

Variant names:

• chr1-153340568-C-T
• rs12063091
• NM_020393.4:c.637G>A

Variant summary

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

The NM_020393.4(PGLYRP4):​c.637G>A​(p.Val213Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 1,613,610 control chromosomes in the GnomAD database, including 3,148 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 0.073 (525 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2623 hom.)
• Consequence: PGLYRP4 NM_020393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 14 publications found

Genes affected

PGLYRP4 (HGNC:30015): (peptidoglycan recognition protein 4) Summary: This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. These proteins are part of the innate immune system and recognize peptidoglycan, a ubiquitous component of bacterial cell walls. This antimicrobial protein binds to murein peptidoglycans of Gram-positive bacteria. [provided by RefSeq, Oct 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034418106).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGLYRP4	NM_020393.4	c.637G>A	p.Val213Ile	missense_variant	Exon 7 of 9	ENST00000359650.10	NP_065126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGLYRP4	ENST00000359650.10	c.637G>A	p.Val213Ile	missense_variant	Exon 7 of 9	1	NM_020393.4	ENSP00000352672.5
PGLYRP4	ENST00000368739.3	c.625G>A	p.Val209Ile	missense_variant	Exon 7 of 9	5		ENSP00000357728.3

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11063 AN: 152052 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0790

GnomAD2 exomes AF: 0.0518 AC: 12930 AN: 249854 AF XY: 0.0514

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0399

Gnomad ASJ exome AF: 0.0677

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.0172

Gnomad NFE exome AF: 0.0578

Gnomad OTH exome AF: 0.0585

GnomAD4 exome AF: 0.0556 AC: 81198 AN: 1461440 Hom.: 2623 Cov.: 32 AF XY: 0.0555 AC XY: 40322 AN XY: 727010

African (AFR) AF: 0.138 AC: 4634 AN: 33462

American (AMR) AF: 0.0424 AC: 1897 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 1743 AN: 26136

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39696

South Asian (SAS) AF: 0.0514 AC: 4430 AN: 86248

European-Finnish (FIN) AF: 0.0204 AC: 1084 AN: 53248

Middle Eastern (MID) AF: 0.107 AC: 615 AN: 5724

European-Non Finnish (NFE) AF: 0.0567 AC: 63089 AN: 1111840

Other (OTH) AF: 0.0611 AC: 3691 AN: 60364

GnomAD4 genome AF: 0.0728 AC: 11082 AN: 152170 Hom.: 525 Cov.: 32 AF XY: 0.0698 AC XY: 5191 AN XY: 74398

African (AFR) AF: 0.134 AC: 5549 AN: 41506

American (AMR) AF: 0.0559 AC: 854 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.0483 AC: 233 AN: 4820

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3845 AN: 67980

Other (OTH) AF: 0.0782 AC: 165 AN: 2110

Alfa AF: 0.0603 Hom.: 1044

Bravo AF: 0.0780

TwinsUK AF: 0.0604 AC: 224

ALSPAC AF: 0.0576 AC: 222

ESP6500AA AF: 0.132 AC: 580

ESP6500EA AF: 0.0599 AC: 515

ExAC AF: 0.0541 AC: 6574

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.0613

EpiControl AF: 0.0689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.26
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.37	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.7	N;.
PhyloP100		0.57
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.68	N;N
REVEL	Benign	0.018
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.047
MPC		0.045
ClinPred		0.000042	T
GERP RS		-0.27
Varity_R		0.028
gMVP		0.081
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12063091; hg19: chr1-153313044; COSMIC: COSV62834876; COSMIC: COSV62834876;