7-111098289-G-T

Variant names:

• chr7-111098289-G-T
• rs10261004
• NM_001099658.2:c.-440-1592G>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.-440-1592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,716 control chromosomes in the GnomAD database, including 42,864 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 0.74 (42864 hom., cov: 32)
• Consequence: LRRN3 NM_001099658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN3	NM_001099658.2	c.-440-1592G>T		intron_variant	Intron 1 of 2	ENST00000308478.10	NP_001093128.1
IMMP2L	NM_032549.4	c.240-134724C>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.-440-1592G>T		intron_variant	Intron 1 of 2	1	NM_001099658.2	ENSP00000312001.5
IMMP2L	ENST00000405709.7	c.240-134724C>A		intron_variant	Intron 3 of 5	1	NM_032549.4	ENSP00000384966.2

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112746 AN: 151598 Hom.: 42857 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.743 AC: 112785 AN: 151716 Hom.: 42864 Cov.: 32 AF XY: 0.746 AC XY: 55309 AN XY: 74144

African (AFR) AF: 0.580 AC: 24007 AN: 41422

American (AMR) AF: 0.808 AC: 12272 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2338 AN: 3464

East Asian (EAS) AF: 0.799 AC: 4108 AN: 5142

South Asian (SAS) AF: 0.756 AC: 3641 AN: 4816

European-Finnish (FIN) AF: 0.843 AC: 8921 AN: 10580

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 54936 AN: 67786

Other (OTH) AF: 0.743 AC: 1569 AN: 2112

Alfa AF: 0.762 Hom.: 8266

Bravo AF: 0.735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.33
PhyloP100		-0.59
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: rs10261004; hg19: chr7-110738345;