7-111123447-A-G

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.675A>G(p.Thr225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,613,528 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (24 hom.)
• Consequence: LRRN3 NM_001099658.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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=-0.88).
• BP6: Variant 7-111123447-A-G is Benign according to our data. Variant chr7-111123447-A-G is described in ClinVar as [Benign]. Clinvar id is 788359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS2: High AC in GnomAd at 445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRN3	NM_001099658.2	c.675A>G	p.Thr225=	synonymous_variant	3/3	ENST00000308478.10
IMMP2L	NM_032549.4	c.240-159882T>C		intron_variant		ENST00000405709.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRN3	ENST00000308478.10	c.675A>G	p.Thr225=	synonymous_variant	3/3	1	NM_001099658.2	P1
IMMP2L	ENST00000405709.7	c.240-159882T>C		intron_variant		1	NM_032549.4	P1

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 445 AN: 152192 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00467

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00279 AC: 697 AN: 250164 Hom.: 2 AF XY: 0.00285 AC XY: 385 AN XY: 135194

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00230

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000886

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00455

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.00421 AC: 6155 AN: 1461218 Hom.: 24 Cov.: 34 AF XY: 0.00411 AC XY: 2986 AN XY: 726912

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.00167

Gnomad4 NFE exome AF: 0.00498

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.00292 AC: 445 AN: 152310 Hom.: 2 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74474

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00468

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00305

EpiCase AF: 0.00568

EpiControl AF: 0.00504

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.34
Dann	Benign	0.56

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: rs35229264; hg19: chr7-110763503;