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GeneBe

7-111123672-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001099658.2(LRRN3):c.900C>T(p.Ile300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,613,832 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

LRRN3
NM_001099658.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53
Variant links:
Genes affected
LRRN3 (HGNC:17200): (leucine rich repeat neuronal 3) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-111123672-C-T is Benign according to our data. Variant chr7-111123672-C-T is described in ClinVar as [Benign]. Clinvar id is 776254.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.53 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 314 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRN3NM_001099658.2 linkuse as main transcriptc.900C>T p.Ile300= synonymous_variant 3/3 ENST00000308478.10
IMMP2LNM_032549.4 linkuse as main transcriptc.240-160107G>A intron_variant ENST00000405709.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRN3ENST00000308478.10 linkuse as main transcriptc.900C>T p.Ile300= synonymous_variant 3/31 NM_001099658.2 P1
IMMP2LENST00000405709.7 linkuse as main transcriptc.240-160107G>A intron_variant 1 NM_032549.4 P1Q96T52-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00206
AC:
314
AN:
152058
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00713
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000787
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000690
AC:
173
AN:
250668
Hom.:
0
AF XY:
0.000524
AC XY:
71
AN XY:
135530
show subpopulations
Gnomad AFR exome
AF:
0.00791
Gnomad AMR exome
AF:
0.000811
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000417
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000270
AC:
394
AN:
1461656
Hom.:
0
Cov.:
34
AF XY:
0.000242
AC XY:
176
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.00825
Gnomad4 AMR exome
AF:
0.000850
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00208
AC:
316
AN:
152176
Hom.:
2
Cov.:
32
AF XY:
0.00199
AC XY:
148
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00715
Gnomad4 AMR
AF:
0.000786
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000203
Hom.:
0
Bravo
AF:
0.00266
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingInvitaeOct 09, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
0.56
Dann
Benign
0.79

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: rs34643951; hg19: chr7-110763728; COSMIC: COSV57819609; COSMIC: COSV57819609; API