7-111123903-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001099658.2(LRRN3):c.1131T>C(p.Arg377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,613,956 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: LRRN3 NM_001099658.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.878

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 7-111123903-T-C is Benign according to our data. Variant chr7-111123903-T-C is described in ClinVar as [Benign]. Clinvar id is 776255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.878 with no splicing effect.
• BS2: High AC in GnomAd at 355 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRN3	NM_001099658.2	c.1131T>C	p.Arg377=	synonymous_variant	3/3	ENST00000308478.10
IMMP2L	NM_032549.4	c.240-160338A>G		intron_variant		ENST00000405709.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRN3	ENST00000308478.10	c.1131T>C	p.Arg377=	synonymous_variant	3/3	1	NM_001099658.2	P1
IMMP2L	ENST00000405709.7	c.240-160338A>G		intron_variant		1	NM_032549.4	P1

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 355 AN: 152128 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000737 AC: 185 AN: 251000 Hom.: 0 AF XY: 0.000531 AC XY: 72 AN XY: 135650

Gnomad AFR exome AF: 0.00917

Gnomad AMR exome AF: 0.000812

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000280 AC: 409 AN: 1461710 Hom.: 0 Cov.: 34 AF XY: 0.000250 AC XY: 182 AN XY: 727154

Gnomad4 AFR exome AF: 0.00917

Gnomad4 AMR exome AF: 0.000829

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152246 Hom.: 3 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74438

Gnomad4 AFR AF: 0.00830

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00156 Hom.: 0

Bravo AF: 0.00295

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.8
Dann	Benign	0.65

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: rs143646592; hg19: chr7-110763959;