chr1-153347896-T-G

Variant names:

• chr1-153347896-T-G
• rs3006458
• NM_020393.4:c.37A>C

Variant summary

Our verdict is Benign. The variant received -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. 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 0.81 (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
• Publications: 40 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=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 rank	MANE	Protein	UniProt
PGLYRP4	NM_020393.4	c.37A>C	p.Ile13Leu	missense_variant	Exon 2 of 9	ENST00000359650.10	NP_065126.2

Ensembl

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

GnomAD2 exomes AF: 0.823 AC: 205999 AN: 250354 AF XY: 0.827

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 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

African (AFR) AF: 0.716 AC: 23927 AN: 33426

American (AMR) AF: 0.801 AC: 35742 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 20866 AN: 26118

East Asian (EAS) AF: 0.722 AC: 28615 AN: 39658

South Asian (SAS) AF: 0.827 AC: 71229 AN: 86124

European-Finnish (FIN) AF: 0.874 AC: 46640 AN: 53388

Middle Eastern (MID) AF: 0.812 AC: 4683 AN: 5764

European-Non Finnish (NFE) AF: 0.855 AC: 948878 AN: 1109880

Other (OTH) AF: 0.834 AC: 50262 AN: 60292

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

African (AFR) AF: 0.717 AC: 29728 AN: 41438

American (AMR) AF: 0.838 AC: 12812 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2789 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3737 AN: 5164

South Asian (SAS) AF: 0.821 AC: 3956 AN: 4820

European-Finnish (FIN) AF: 0.875 AC: 9266 AN: 10590

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58023 AN: 67980

Other (OTH) AF: 0.819 AC: 1718 AN: 2098

Alfa AF: 0.832 Hom.: 99075

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
PhyloP100		0.19
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
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: rs3006458; hg19: chr1-153320372; COSMIC: COSV62834828;