11-40115617-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001258419.2(LRRC4C):c.676C>A(p.Leu226Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000445 in 1,461,884 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: not found (cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
LRRC4C
NM_001258419.2 missense
NM_001258419.2 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 6.24
Genes affected
LRRC4C (HGNC:29317): (leucine rich repeat containing 4C) NGL1 is a specific binding partner for netrin G1 (NTNG1; MIM 608818), which is a member of the netrin family of axon guidance molecules (Lin et al., 2003 [PubMed 14595443]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, LRRC4C
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27665842).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC4C | NM_001258419.2 | c.676C>A | p.Leu226Ile | missense_variant | 7/7 | ENST00000528697.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC4C | ENST00000528697.6 | c.676C>A | p.Leu226Ile | missense_variant | 7/7 | 1 | NM_001258419.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250916Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135580
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727242
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GnomAD4 genome ? Cov.: 32
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32
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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 | Jan 06, 2023 | The c.676C>A (p.L226I) alteration is located in exon 2 (coding exon 1) of the LRRC4C gene. This alteration results from a C to A substitution at nucleotide position 676, causing the leucine (L) at amino acid position 226 to be replaced by an isoleucine (I). 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
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N
REVEL
Benign
Sift
Benign
T;.;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;B;B
Vest4
MutPred
Gain of catalytic residue at L231 (P = 0.0347);Gain of catalytic residue at L231 (P = 0.0347);Gain of catalytic residue at L231 (P = 0.0347);Gain of catalytic residue at L231 (P = 0.0347);Gain of catalytic residue at L231 (P = 0.0347);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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