GeneBe

rs752420006

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080460.3(LRRIQ4):​c.13A>C​(p.Ile5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRRIQ4
NM_001080460.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.628

Publications

0 publications found
Variant links:
Genes affected
LRRIQ4 (HGNC:34298): (leucine rich repeats and IQ motif containing 4) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04589227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080460.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRRIQ4
NM_001080460.3
MANE Select
c.13A>Cp.Ile5Leu
missense
Exon 2 of 6NP_001073929.1A6NIV6

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRRIQ4
ENST00000340806.7
TSL:5 MANE Select
c.13A>Cp.Ile5Leu
missense
Exon 2 of 6ENSP00000342188.6A6NIV6
LRRIQ4
ENST00000691416.1
c.13A>Cp.Ile5Leu
missense
Exon 2 of 5ENSP00000508855.1A0A8I5KNZ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1318884
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
642980
African (AFR)
AF:
0.00
AC:
0
AN:
29130
American (AMR)
AF:
0.00
AC:
0
AN:
22986
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19102
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36346
South Asian (SAS)
AF:
0.00
AC:
0
AN:
59132
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48666
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5154
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1044412
Other (OTH)
AF:
0.00
AC:
0
AN:
53956
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.085
DANN
Benign
0.54
DEOGEN2
Benign
0.00064
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.28
N
PhyloP100
-0.63
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.10
N
REVEL
Benign
0.0050
Sift
Benign
0.56
T
Sift4G
Benign
0.94
T
Polyphen
0.0
B
Vest4
0.14
MutPred
0.50
Loss of catalytic residue at I5 (P = 0.0016)
MVP
0.061
MPC
0.10
ClinPred
0.039
T
GERP RS
-4.0
Varity_R
0.046
gMVP
0.075
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs752420006; hg19: chr3-169539722; API