Genetic Variant LONRF2:p.His482Asn (chr2-100298868-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198461.4(LONRF2):c.1444C>A(p.His482Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,614,110 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 79 hom. )

Consequence

LONRF2
NM_198461.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00684464).

BP6

Variant 2-100298868-G-T is Benign according to our data. Variant chr2-100298868-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651206.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198461.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF2	NM_198461.4	MANE Select	c.1444C>A	p.His482Asn	missense	Exon 7 of 12	NP_940863.3	Q1L5Z9-1
	LONRF2	NM_001371783.1		c.715C>A	p.His239Asn	missense	Exon 8 of 13	NP_001358712.1	Q1L5Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF2	ENST00000393437.8	TSL:5 MANE Select	c.1444C>A	p.His482Asn	missense	Exon 7 of 12	ENSP00000377086.3	Q1L5Z9-1
	LONRF2	ENST00000409647.1	TSL:2	c.715C>A	p.His239Asn	missense	Exon 7 of 12	ENSP00000386823.1	Q1L5Z9-2

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1069

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00977

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00730

AC:

1836

AN:

251478

AF XY:

0.00731

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00942

AC:

13771

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00914

AC XY:

6645

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

33480

American (AMR)

AF:

0.00385

AC:

172

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00536

AC:

140

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000974

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0193

AC:

1031

AN:

53420

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0107

AC:

11882

AN:

1111918

Other (OTH)

AF:

0.00672

AC:

406

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

684

1368

2052

2736

3420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00702

AC:

1069

AN:

152316

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

533

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41574

American (AMR)

AF:

0.00425

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0210

AC:

223

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00976

AC:

664

AN:

68032

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00818

Hom.:

Bravo

AF:

0.00585

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00742

AC:

901

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00936

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.4

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.023

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.42

PhyloP100

1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.2

REVEL

Benign

0.049

Sift

Benign

0.17

Sift4G

Benign

0.52

Polyphen

0.0030

Vest4

0.21

MVP

0.30

MPC

0.39

ClinPred

0.016

GERP RS

2.1

Varity_R

0.080

gMVP

0.33

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over