7-100575168-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000310300.11(LRCH4):c.1991T>G(p.Val664Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
Consequence
LRCH4
ENST00000310300.11 missense
ENST00000310300.11 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
LRCH4 (HGNC:6691): (leucine rich repeats and calponin homology domain containing 4) This gene encodes a protein that contains leucine-rich repeats (LRR) at its amino terminus and that is known to be involved in ligand binding. The carboxyl terminus may act as a membrane anchor. Identified structural elements suggest that the encoded protein resembles a receptor. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16721833).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRCH4 | NM_002319.5 | c.1991T>G | p.Val664Gly | missense_variant | 18/18 | ENST00000310300.11 | NP_002310.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRCH4 | ENST00000310300.11 | c.1991T>G | p.Val664Gly | missense_variant | 18/18 | 1 | NM_002319.5 | ENSP00000309689 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248986Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134976
GnomAD3 exomes
AF:
AC:
1
AN:
248986
Hom.:
AF XY:
AC XY:
1
AN XY:
134976
Gnomad AFR exome
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Aug 12, 2021 | The c.1991T>G (p.V664G) alteration is located in exon 18 (coding exon 18) of the LRCH4 gene. This alteration results from a T to G substitution at nucleotide position 1991, causing the valine (V) at amino acid position 664 to be replaced by a glycine (G). 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
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Uncertain
.;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.072
.;B;.
Vest4
MutPred
0.34
.;Loss of sheet (P = 0.0025);.;
MVP
MPC
0.10
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at