chr19-4538587-G-A

Variant names:

• chr19-4538587-G-A
• rs966384
• NM_052972.3:c.397C>T

Variant summary

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

The NM_052972.3(LRG1):​c.397C>T​(p.Pro133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,612,742 control chromosomes in the GnomAD database, including 94,543 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 0.30 (7724 hom., cov: 33)
  • Exomes 𝑓: 0.34 (86819 hom.)
• Consequence: LRG1 NM_052972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 44 publications found

Genes affected

LRG1 (HGNC:29480): (leucine rich alpha-2-glycoprotein 1) The leucine-rich repeat (LRR) family of proteins, including LRG1, have been shown to be involved in protein-protein interaction, signal transduction, and cell adhesion and development. LRG1 is expressed during granulocyte differentiation (O'Donnell et al., 2002 [PubMed 12223515]).[supplied by OMIM, Mar 2008]

ENSG00000267385 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.4779254E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052972.3. 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
	LRG1	NM_052972.3	MANE Select	c.397C>T	p.Pro133Ser	missense	Exon 2 of 2	NP_443204.1	P02750

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRG1	ENST00000306390.7	TSL:1 MANE Select	c.397C>T	p.Pro133Ser	missense	Exon 2 of 2	ENSP00000302621.4	P02750
	ENSG00000267385	ENST00000586020.1	TSL:2	n.32+1395C>T		intron	N/A	ENSP00000464793.1	K7EIL1
	LRG1	ENST00000885090.1		c.367C>T	p.Pro123Ser	missense	Exon 2 of 2	ENSP00000555149.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45007 AN: 152038 Hom.: 7718 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.369 AC: 91268 AN: 247218 AF XY: 0.362

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.541

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.339 AC: 494579 AN: 1460586 Hom.: 86819 Cov.: 58 AF XY: 0.337 AC XY: 245101 AN XY: 726448

African (AFR) AF: 0.114 AC: 3828 AN: 33472

American (AMR) AF: 0.495 AC: 22120 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 8254 AN: 26132

East Asian (EAS) AF: 0.496 AC: 19679 AN: 39684

South Asian (SAS) AF: 0.317 AC: 27355 AN: 86244

European-Finnish (FIN) AF: 0.422 AC: 22283 AN: 52748

Middle Eastern (MID) AF: 0.280 AC: 1614 AN: 5756

European-Non Finnish (NFE) AF: 0.333 AC: 369638 AN: 1111482

Other (OTH) AF: 0.328 AC: 19808 AN: 60354

GnomAD4 genome AF: 0.296 AC: 45035 AN: 152156 Hom.: 7724 Cov.: 33 AF XY: 0.304 AC XY: 22587 AN XY: 74386

African (AFR) AF: 0.125 AC: 5182 AN: 41540

American (AMR) AF: 0.394 AC: 6015 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2707 AN: 5158

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4512 AN: 10576

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22917 AN: 67984

Other (OTH) AF: 0.304 AC: 643 AN: 2116

Alfa AF: 0.326 Hom.: 32930

Bravo AF: 0.290

TwinsUK AF: 0.321 AC: 1189

ALSPAC AF: 0.336 AC: 1295

ESP6500AA AF: 0.129 AC: 566

ESP6500EA AF: 0.324 AC: 2767

ExAC AF: 0.356 AC: 43143

Asia WGS AF: 0.405 AC: 1411 AN: 3478

EpiCase AF: 0.327

EpiControl AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.000085	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.089
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.080
Sift	Benign	0.18	T
Sift4G	Benign	0.47	T
Polyphen		0.27	B
Vest4		0.017
MPC		0.085
ClinPred		0.012	T
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.41
Mutation Taster		=97/3	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: rs966384; hg19: chr19-4538599; COSMIC: COSV56702259; COSMIC: COSV56702259;