Variant chr2-77519713-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001134745.3(LRRTM4):c.156C>G(p.Phe52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,613,336 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 9 hom. )

Consequence

LRRTM4
NM_001134745.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.441

Variant links:

Genes affected

LRRTM4 (HGNC:19411): (leucine rich repeat transmembrane neuronal 4) Predicted to enable heparan sulfate proteoglycan binding activity. Predicted to be involved in regulation of synapse assembly. Predicted to act upstream of or within AMPA glutamate receptor clustering; positive regulation of synapse assembly; and regulation of presynaptic membrane organization. Predicted to be located in postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular matrix; extracellular space; and glutamatergic synapse. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRTM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005299151).

BP6

Variant 2-77519713-G-C is Benign according to our data. Variant chr2-77519713-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034583.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRTM4	NM_001134745.3 linkuse as main transcript	c.156C>G	p.Phe52Leu	missense_variant	3/4	ENST00000409884.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRTM4	ENST00000409884.6 linkuse as main transcript	c.156C>G	p.Phe52Leu	missense_variant	3/4	1	NM_001134745.3	P4	Q86VH4-1

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

628

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

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:

0.00384

GnomAD3 exomes

AF:

0.000914

AC:

227

AN:

248464

Hom.:

AF XY:

0.000668

AC XY:

AN XY:

134764

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.000407

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:

0.00000890

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000415

AC:

606

AN:

1461260

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

246

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.000470

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:

0.0000117

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00414

AC:

629

AN:

152076

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

321

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000598

Hom.:

Bravo

AF:

0.00466

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000968

AC:

117

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LRRTM4-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0030

T;T;T;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.87

D;.;D;D;D

MetaRNN

Benign

0.0053

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.80

.;N;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.35

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.89

T;T;T;T;T

Polyphen

0.12, 0.19

.;B;B;B;B

Vest4

0.51

MutPred

0.56

.;Loss of catalytic residue at D54 (P = 0.1151);Loss of catalytic residue at D54 (P = 0.1151);Loss of catalytic residue at D54 (P = 0.1151);.;

MVP

0.11

MPC

1.6

ClinPred

0.023

GERP RS

-0.18

Varity_R

0.10

gMVP

0.55

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

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