7-100575168-A-C

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

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68
Variant links:
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
LRCH4NM_002319.5 linkuse as main transcriptc.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
LRCH4ENST00000310300.11 linkuse as main transcriptc.1991T>G p.Val664Gly missense_variant 18/181 NM_002319.5 ENSP00000309689 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248986
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134976
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:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
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 submitterclinical testingAmbry GeneticsAug 12, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
23
DANN
Benign
0.97
DEOGEN2
Benign
0.031
T;T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.42
T;T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;N;.
MutationTaster
Benign
0.98
D;D
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.1
.;N;N
REVEL
Benign
0.060
Sift
Uncertain
0.0040
.;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.072
.;B;.
Vest4
0.17
MutPred
0.34
.;Loss of sheet (P = 0.0025);.;
MVP
0.48
MPC
0.10
ClinPred
0.40
T
GERP RS
4.2
Varity_R
0.18
gMVP
0.54

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.

Other links and lift over

dbSNP: rs780059053; hg19: chr7-100172791; API