Genetic Variant LONRF2:p.Gly377Gly (chr2-100299853-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_198461.4(LONRF2):c.1131T>C(p.Gly377Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,608,764 control chromosomes in the GnomAD database, including 161,418 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 0.34 ( 10897 hom., cov: 31)

Exomes 𝑓: 0.45 ( 150521 hom. )

Consequence

LONRF2
NM_198461.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.818

Publications

24 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=0.818 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

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.1131T>C	p.Gly377Gly	synonymous	Exon 5 of 12	NP_940863.3	Q1L5Z9-1
	LONRF2	NM_001371783.1		c.402T>C	p.Gly134Gly	synonymous	Exon 6 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.1131T>C	p.Gly377Gly	synonymous	Exon 5 of 12	ENSP00000377086.3	Q1L5Z9-1
	LONRF2	ENST00000409647.1	TSL:2	c.402T>C	p.Gly134Gly	synonymous	Exon 5 of 12	ENSP00000386823.1	Q1L5Z9-2

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51678

AN:

151702

Hom.:

10905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.298

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.346

GnomAD2 exomes

AF:

0.385

AC:

96478

AN:

250802

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.0822

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.503

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.445

AC:

648434

AN:

1456944

Hom.:

150521

Cov.:

AF XY:

0.442

AC XY:

320461

AN XY:

725112

show subpopulations

African (AFR)

AF:

0.0760

AC:

2542

AN:

33440

American (AMR)

AF:

0.216

AC:

9651

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

9391

AN:

26112

East Asian (EAS)

AF:

0.487

AC:

19321

AN:

39670

South Asian (SAS)

AF:

0.301

AC:

25924

AN:

86130

European-Finnish (FIN)

AF:

0.499

AC:

26656

AN:

53404

Middle Eastern (MID)

AF:

0.322

AC:

1848

AN:

5736

European-Non Finnish (NFE)

AF:

0.476

AC:

527551

AN:

1107574

Other (OTH)

AF:

0.424

AC:

25550

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

16987

33975

50962

67950

84937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15336

30672

46008

61344

76680

<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:

0.340

AC:

51664

AN:

151820

Hom.:

10897

Cov.:

AF XY:

0.341

AC XY:

25251

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.0933

AC:

3869

AN:

41478

American (AMR)

AF:

0.286

AC:

4359

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1268

AN:

3468

East Asian (EAS)

AF:

0.499

AC:

2568

AN:

5146

South Asian (SAS)

AF:

0.301

AC:

1447

AN:

4804

European-Finnish (FIN)

AF:

0.510

AC:

5355

AN:

10496

Middle Eastern (MID)

AF:

0.283

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.467

AC:

31730

AN:

67872

Other (OTH)

AF:

0.346

AC:

730

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1512

3024

4536

6048

7560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.398

Hom.:

15349

Bravo

AF:

0.313

Asia WGS

AF:

0.371

AC:

1286

AN:

3476

EpiCase

AF:

0.451

EpiControl

AF:

0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.8

(source)

DANN

Benign

0.64

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism (auto)

(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

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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