13-46692576-C-T
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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
NM_001164211.2 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 3.59
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]
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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 |
---|---|---|---|---|---|---|---|---|
LRCH1 | NM_001164211.2 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
LRCH1 | ENST00000389797.8 | c.1055C>T | p.Ser352Leu | missense_variant | 8/20 | 1 | NM_001164211.2 | ENSP00000374447 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 250992Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135622
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GnomAD4 exome AF: 0.000234 AC: 342AN: 1461746Hom.: 0 Cov.: 30 AF XY: 0.000242 AC XY: 176AN XY: 727178
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GnomAD4 genome AF: 0.000342 AC: 52AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74370
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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 21, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;D;.;.
Vest4
MVP
MPC
0.81
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at