13-46692576-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001164211.2(LRCH1):​c.1055C>T​(p.Ser352Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000244 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

LRCH1
NM_001164211.2 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.32351822).
BS2
High AC in GnomAd4 at 52 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRCH1NM_001164211.2 linkuse as main transcriptc.1055C>T p.Ser352Leu missense_variant 8/20 ENST00000389797.8 NP_001157683.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRCH1ENST00000389797.8 linkuse as main transcriptc.1055C>T p.Ser352Leu missense_variant 8/201 NM_001164211.2 ENSP00000374447 Q9Y2L9-3

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000720
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000155
AC:
39
AN:
250992
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000309
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000234
AC:
342
AN:
1461746
Hom.:
0
Cov.:
30
AF XY:
0.000242
AC XY:
176
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000295
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000342
AC:
52
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000720
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000486
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000157
AC:
19
EpiCase
AF:
0.000382
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 21, 2022The c.1055C>T (p.S352L) alteration is located in exon 8 (coding exon 8) of the LRCH1 gene. This alteration results from a C to T substitution at nucleotide position 1055, causing the serine (S) at amino acid position 352 to be replaced by a leucine (L). 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
Benign
0.22
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
.;T;.;T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.29
T;T;T;T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.6
M;M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.3
D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.94
P;D;.;.
Vest4
0.45
MVP
0.42
MPC
0.81
ClinPred
0.34
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs202211483; hg19: chr13-47266711; API