dbSNP rs1193220953: LRRN4CL:p.Val215Leu (chr11-62687866-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203422.4(LRRN4CL):c.643G>C(p.Val215Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,442,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V215M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LRRN4CL
NM_203422.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0980

Publications

0 publications found

Variant links:

Genes affected

LRRN4CL (HGNC:33724): (LRRN4 C-terminal like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRN4CL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10006806).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203422.4. 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
	LRRN4CL	NM_203422.4	MANE Select	c.643G>C	p.Val215Leu	missense	Exon 2 of 2	NP_981967.1	Q8ND94

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN4CL	ENST00000317449.5	TSL:1 MANE Select	c.643G>C	p.Val215Leu	missense	Exon 2 of 2	ENSP00000325808.4	Q8ND94
	LRRN4CL	ENST00000961805.1		c.643G>C	p.Val215Leu	missense	Exon 2 of 2	ENSP00000631864.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1289952

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

627992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26496

American (AMR)

AF:

0.000166

AC:

AN:

18060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18414

East Asian (EAS)

AF:

0.00

AC:

AN:

33012

South Asian (SAS)

AF:

0.0000159

AC:

AN:

62912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36350

Middle Eastern (MID)

AF:

0.000216

AC:

AN:

4626

European-Non Finnish (NFE)

AF:

0.00000772

AC:

AN:

1036784

Other (OTH)

AF:

0.0000188

AC:

AN:

53298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.46

M_CAP

Benign

0.023

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.098

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.74

REVEL

Benign

0.025

Sift

Benign

0.29

Sift4G

Benign

0.76

Polyphen

0.0050

Vest4

0.089

MutPred

0.33

Loss of helix (P = 0.079)

MVP

0.31

MPC

0.36

ClinPred

0.17

GERP RS

3.4

Varity_R

0.053

gMVP

0.60

Mutation Taster

=85/15

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