7-111098289-G-T

Position:

• chr7-111098289-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LRRN3	NM_001099658.2	c.-440-1592G>T		intron_variant		ENST00000308478.10	NP_001093128.1
IMMP2L	NM_032549.4	c.240-134724C>A		intron_variant		ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRN3	ENST00000308478.10	c.-440-1592G>T		intron_variant		1	NM_001099658.2	ENSP00000312001	P1
IMMP2L	ENST00000405709.7	c.240-134724C>A		intron_variant		1	NM_032549.4	ENSP00000384966	P1

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

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.743

Alfa AF: 0.768 Hom.: 8140

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

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

Other links and lift over

dbSNP: rs10261004; hg19: chr7-110738345;