Variant 20-6041158-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152611.5(LRRN4):c.2087C>T(p.Ala696Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,604,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LRRN4
NM_152611.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

LRRN4 (HGNC:16208): (leucine rich repeat neuronal 4) Predicted to be involved in long-term memory. Predicted to act upstream of or within visual learning. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LRRN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04826668).

BP6

Variant 20-6041158-G-A is Benign according to our data. Variant chr20-6041158-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3121190.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRN4	NM_152611.5 linkuse as main transcript	c.2087C>T	p.Ala696Val	missense_variant	5/5	ENST00000378858.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRN4	ENST00000378858.5 linkuse as main transcript	c.2087C>T	p.Ala696Val	missense_variant	5/5	1	NM_152611.5	P1
LRRN4	ENST00000698795.1 linkuse as main transcript	c.*1244C>T		3_prime_UTR_variant	5/5
LRRN4	ENST00000698796.1 linkuse as main transcript	n.2378C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000310

AC:

AN:

226160

Hom.:

AF XY:

0.0000484

AC XY:

AN XY:

123856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000921

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000405

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1451970

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

721656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000415

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.1

DANN

Benign

0.84

DEOGEN2

Benign

0.00071

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.57

M_CAP

Benign

0.0092

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MutPred

0.39

Gain of sheet (P = 0.0827);

MVP

0.11

MPC

0.41

ClinPred

0.058

GERP RS

-1.1

Varity_R

0.021

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over