19-4538587-G-C

Position:

• chr19-4538587-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052972.3(LRG1):​c.397C>G​(p.Pro133Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P133S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRG1 NM_052972.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058849365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRG1	NM_052972.3	c.397C>G	p.Pro133Ala	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	c.397C>G	p.Pro133Ala	missense_variant	2/2	1	NM_052972.3	ENSP00000302621	P1
LRG1	ENST00000586883.1	n.458C>G		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.64
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.012	B
Vest4		0.073
MutPred		0.34		Loss of catalytic residue at P132 (P = 0.0144);
MVP		0.32
MPC		0.066
ClinPred		0.14	T
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.35

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: rs966384; hg19: chr19-4538599;