Genetic Variant LONRF1:p.Ala723Thr (chr8-12723251-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152271.5(LONRF1):c.2167G>A(p.Ala723Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LONRF1
NM_152271.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

Publications

0 publications found

Variant links:

Genes affected

LONRF1 (HGNC:26302): (LON peptidase N-terminal domain and ring finger 1) Predicted to enable metal ion binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LONRF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018459618).

BP6

Variant 8-12723251-C-T is Benign according to our data. Variant chr8-12723251-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3867662.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152271.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LONRF1	NM_152271.5	MANE Select	c.2167G>A	p.Ala723Thr	missense	Exon 12 of 12	NP_689484.3
LONRF1	NM_001329976.2		c.2134G>A	p.Ala712Thr	missense	Exon 12 of 12	NP_001316905.1	Q17RB8-2
LONRF1	NR_138255.2		n.2151G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LONRF1	ENST00000398246.8	TSL:5 MANE Select	c.2167G>A	p.Ala723Thr	missense	Exon 12 of 12	ENSP00000381298.3	Q17RB8-1
LONRF1	ENST00000525024.5	TSL:1	c.445G>A	p.Ala149Thr	missense	Exon 4 of 4	ENSP00000436770.1	E9PQH4
LONRF1	ENST00000526680.5	TSL:1	n.*1005G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000434090.1	E9PRX6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

236514

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32884

American (AMR)

AF:

0.00

AC:

AN:

42338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25588

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

84426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109652

Other (OTH)

AF:

0.0000167

AC:

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.0

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.34

M_CAP

Benign

0.0029

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.8

PhyloP100

2.1

PrimateAI

Benign

0.30

PROVEAN

Benign

1.5

REVEL

Benign

0.064

Sift

Benign

0.96

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MVP

0.082

MPC

0.62

ClinPred

0.032

GERP RS

1.0

Varity_R

0.017

gMVP

0.086

Mutation Taster

=95/5

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over