Variant 19-4538587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000306390.7(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. 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: 𝑓 0.30 ( 7724 hom., cov: 33)

Exomes 𝑓: 0.34 ( 86819 hom. )

Consequence

LRG1
ENST00000306390.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0890

Variant links:

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]

LRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRG1	NM_052972.3 linkuse as main transcript	c.397C>T	p.Pro133Ser	missense_variant	2/2	ENST00000306390.7	NP_443204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRG1	ENST00000306390.7 linkuse as main transcript	c.397C>T	p.Pro133Ser	missense_variant	2/2	1	NM_052972.3	ENSP00000302621	P1
LRG1	ENST00000586883.1 linkuse as main transcript	n.458C>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45007

AN:

152038

Hom.:

7718

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.369

AC:

91268

AN:

247218

Hom.:

18232

AF XY:

0.362

AC XY:

48713

AN XY:

134444

show subpopulations

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 SAS exome

AF:

0.316

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.:

AF XY:

0.337

AC XY:

245101

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.422

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.296

AC:

45035

AN:

152156

Hom.:

7724

Cov.:

AF XY:

0.304

AC XY:

22587

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.333

Hom.:

16840

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.1

DANN

Benign

0.91

DEOGEN2

Benign

0.026

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.24

MetaRNN

Benign

0.000085

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

REVEL

Benign

0.080

Sift

Benign

0.18

Sift4G

Benign

0.47

Polyphen

0.27

Vest4

0.017

MPC

0.085

ClinPred

0.012

GERP RS

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over