1-153347896-T-G

Position:

• chr1-153347896-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020393.4(PGLYRP4):​c.37A>C​(p.Ile13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,611,302 control chromosomes in the GnomAD database, including 570,217 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.81 (50123 hom., cov: 31)
  • Exomes 𝑓: 0.84 (520094 hom.)
• Consequence: PGLYRP4 NM_020393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.349188E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP4	NM_020393.4	c.37A>C	p.Ile13Leu	missense_variant	2/9	ENST00000359650.10	NP_065126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP4	ENST00000359650.10	c.37A>C	p.Ile13Leu	missense_variant	2/9	1	NM_020393.4	ENSP00000352672.5
PGLYRP4	ENST00000368739.3	c.37A>C	p.Ile13Leu	missense_variant	2/9	5		ENSP00000357728.3
PGLYRP4	ENST00000490266.1	n.83A>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123000 AN: 151938 Hom.: 50103 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.817

GnomAD3 exomes AF: 0.823 AC: 205999 AN: 250354 Hom.: 85097 AF XY: 0.827 AC XY: 111939 AN XY: 135350

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.794

Gnomad ASJ exome AF: 0.799

Gnomad EAS exome AF: 0.716

Gnomad SAS exome AF: 0.835

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.835

GnomAD4 exome AF: 0.843 AC: 1230842 AN: 1459246 Hom.: 520094 Cov.: 38 AF XY: 0.843 AC XY: 612398 AN XY: 726050

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.827

Gnomad4 FIN exome AF: 0.874

Gnomad4 NFE exome AF: 0.855

Gnomad4 OTH exome AF: 0.834

GnomAD4 genome AF: 0.809 AC: 123065 AN: 152056 Hom.: 50123 Cov.: 31 AF XY: 0.811 AC XY: 60286 AN XY: 74352

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.819

Alfa AF: 0.839 Hom.: 64376

Bravo AF: 0.801

TwinsUK AF: 0.853 AC: 3162

ALSPAC AF: 0.860 AC: 3315

ESP6500AA AF: 0.732 AC: 3223

ESP6500EA AF: 0.848 AC: 7289

ExAC AF: 0.823 AC: 99869

Asia WGS AF: 0.772 AC: 2684 AN: 3478

EpiCase AF: 0.852

EpiControl AF: 0.845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.50
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00051	N
LIST_S2	Benign	0.17	T;T
MetaRNN	Benign	6.3e-7	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.9	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.022
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.11
MPC		0.052
ClinPred		0.00036	T
GERP RS		-1.1
Varity_R		0.043
gMVP		0.23

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

Other links and lift over

dbSNP: rs3006458; hg19: chr1-153320372; COSMIC: COSV62834828;