7-111106552-C-T

Variant names:

• chr7-111106552-C-T
• rs214884
• NM_001099658.2:c.-359+6590C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099658.2(LRRN3):​c.-359+6590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 151,492 control chromosomes in the GnomAD database, including 60,556 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60556 hom., cov: 28)
• Consequence: LRRN3 NM_001099658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN3	NM_001099658.2	c.-359+6590C>T		intron_variant	Intron 2 of 2	ENST00000308478.10	NP_001093128.1
IMMP2L	NM_032549.4	c.240-142987G>A		intron_variant	Intron 3 of 5	ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN3	ENST00000308478.10	c.-359+6590C>T		intron_variant	Intron 2 of 2	1	NM_001099658.2	ENSP00000312001.5
IMMP2L	ENST00000405709.7	c.240-142987G>A		intron_variant	Intron 3 of 5	1	NM_032549.4	ENSP00000384966.2

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135257 AN: 151374 Hom.: 60506 Cov.: 28

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.884

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.894 AC: 135365 AN: 151492 Hom.: 60556 Cov.: 28 AF XY: 0.892 AC XY: 66007 AN XY: 73980

African (AFR) AF: 0.869 AC: 35903 AN: 41336

American (AMR) AF: 0.906 AC: 13714 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2837 AN: 3466

East Asian (EAS) AF: 0.926 AC: 4790 AN: 5170

South Asian (SAS) AF: 0.867 AC: 4157 AN: 4794

European-Finnish (FIN) AF: 0.903 AC: 9495 AN: 10512

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.908 AC: 61544 AN: 67776

Other (OTH) AF: 0.883 AC: 1857 AN: 2102

Alfa AF: 0.901 Hom.: 98256

Bravo AF: 0.894

Asia WGS AF: 0.880 AC: 3056 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.20
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs214884; hg19: chr7-110746608;