chr3-46532867-T-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_024512.5(LRRC2):c.533A>C(p.Tyr178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,614,010 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0045 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 1 hom. )
Consequence
LRRC2
NM_024512.5 missense
NM_024512.5 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: -0.0300
Genes affected
LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008144259).
BP6
?
Variant 3-46532867-T-G is Benign according to our data. Variant chr3-46532867-T-G is described in ClinVar as [Benign]. Clinvar id is 731673.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000545 (797/1461668) while in subpopulation AFR AF= 0.0161 (540/33468). AF 95% confidence interval is 0.015. There are 1 homozygotes in gnomad4_exome. There are 359 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRC2 | NM_024512.5 | c.533A>C | p.Tyr178Ser | missense_variant | 5/9 | ENST00000395905.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRC2 | ENST00000395905.8 | c.533A>C | p.Tyr178Ser | missense_variant | 5/9 | 1 | NM_024512.5 | P1 | |
LRRC2 | ENST00000296144.3 | c.533A>C | p.Tyr178Ser | missense_variant | 5/9 | 1 | P1 | ||
LRRC2 | ENST00000682605.1 | c.533A>C | p.Tyr178Ser | missense_variant | 5/9 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00450 AC: 685AN: 152224Hom.: 11 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00128 AC: 321AN: 251276Hom.: 2 AF XY: 0.00104 AC XY: 141AN XY: 135798
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GnomAD4 exome AF: 0.000545 AC: 797AN: 1461668Hom.: 1 Cov.: 33 AF XY: 0.000494 AC XY: 359AN XY: 727130
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GnomAD4 genome ? AF: 0.00451 AC: 687AN: 152342Hom.: 11 Cov.: 32 AF XY: 0.00460 AC XY: 343AN XY: 74500
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179
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2018 | - - |
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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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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