Variant 13-46553538-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001164211.2(LRCH1):c.142G>C(p.Gly48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,394,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

LRCH1
NM_001164211.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.609

Variant links:

Genes affected

LRCH1 (HGNC:20309): (leucine rich repeats and calponin homology domain containing 1) This gene encodes a protein with a leucine-rich repeat and a calponin homology domain. Polymorphism in this gene may be associated with susceptibililty to knee osteoarthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2010]

LRCH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2294868).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH1	NM_001164211.2 linkuse as main transcript	c.142G>C	p.Gly48Arg	missense_variant	1/20	ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8 linkuse as main transcript	c.142G>C	p.Gly48Arg	missense_variant	1/20	1	NM_001164211.2	ENSP00000374447		Q9Y2L9-3
LRCH1	ENST00000389798.7 linkuse as main transcript	c.142G>C	p.Gly48Arg	missense_variant	1/19	1		ENSP00000374448	A1	Q9Y2L9-1
LRCH1	ENST00000311191.10 linkuse as main transcript	c.142G>C	p.Gly48Arg	missense_variant	1/19	1		ENSP00000308493	P3	Q9Y2L9-2
LRCH1	ENST00000443945.6 linkuse as main transcript	n.369G>C		non_coding_transcript_exon_variant	1/13	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000675

AC:

AN:

148230

Hom.:

AF XY:

0.00

AC XY:

AN XY:

79014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1394098

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

687272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000195

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.142G>C (p.G48R) alteration is located in exon 1 (coding exon 1) of the LRCH1 gene. This alteration results from a G to C substitution at nucleotide position 142, causing the glycine (G) at amino acid position 48 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0069

.;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.80

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.080

Sift

Benign

0.031

D;D;D

Sift4G

Benign

0.55

T;T;T

Polyphen

0.57

P;B;.

Vest4

0.38

MutPred

0.42

Gain of catalytic residue at S52 (P = 0);Gain of catalytic residue at S52 (P = 0);Gain of catalytic residue at S52 (P = 0);

MVP

0.40

MPC

0.94

ClinPred

0.67

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.093

gMVP

0.31

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over