Genetic Variant NM_198461.4:c.1131T>C (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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LONRF2	NM_198461.4 link	c.1131T>C	p.Gly377Gly	synonymous_variant	Exon 5 of 12	ENST00000393437.8	NP_940863.3	Q1L5Z9-1
LONRF2	NM_001371783.1 link	c.402T>C	p.Gly134Gly	synonymous_variant	Exon 6 of 13		NP_001358712.1
LONRF2	XM_047443537.1 link	c.402T>C	p.Gly134Gly	synonymous_variant	Exon 5 of 12		XP_047299493.1
LONRF2	XM_047443538.1 link	c.1131T>C	p.Gly377Gly	synonymous_variant	Exon 5 of 6		XP_047299494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LONRF2	ENST00000393437.8 link	c.1131T>C	p.Gly377Gly	synonymous_variant	Exon 5 of 12	5	NM_198461.4	ENSP00000377086.3		Q1L5Z9-1
LONRF2	ENST00000409647.1 link	c.402T>C	p.Gly134Gly	synonymous_variant	Exon 5 of 12	2		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

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

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 v4.3

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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NM_198461.4:c.1131T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over