Variant 2-100295518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_198461.4(LONRF2):c.1512G>A(p.Leu504Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,613,462 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 55 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 37 hom. )

Consequence

LONRF2
NM_198461.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.806

Variant links:

Genes affected

LONRF2 (HGNC:24788): (LON peptidase N-terminal domain and ring finger 2) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LONRF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-100295518-C-T is Benign according to our data. Variant chr2-100295518-C-T is described in ClinVar as [Benign]. Clinvar id is 711331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.806 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1950/152208) while in subpopulation AFR AF= 0.0447 (1857/41508). AF 95% confidence interval is 0.043. There are 55 homozygotes in gnomad4. There are 908 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF2	NM_198461.4 link	c.1512G>A	p.Leu504Leu	synonymous_variant	8/12	ENST00000393437.8	NP_940863.3	Q1L5Z9-1
LONRF2	NM_001371783.1 link	c.783G>A	p.Leu261Leu	synonymous_variant	9/13		NP_001358712.1
LONRF2	XM_047443537.1 link	c.783G>A	p.Leu261Leu	synonymous_variant	8/12		XP_047299493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF2	ENST00000393437.8 link	c.1512G>A	p.Leu504Leu	synonymous_variant	8/12	5	NM_198461.4	ENSP00000377086.3		Q1L5Z9-1
LONRF2	ENST00000409647.1 link	c.783G>A	p.Leu261Leu	synonymous_variant	8/12	2		ENSP00000386823.1		Q1L5Z9-2

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1945

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00338

AC:

848

AN:

250994

Hom.:

AF XY:

0.00254

AC XY:

344

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.0469

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00139

AC:

2030

AN:

1461254

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

862

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.0505

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.0128

AC:

1950

AN:

152208

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0447

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00601

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.5

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over