rs35997283

Positions:

chr4-109870370-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_198506.5(LRIT3):c.1621A>G(p.Ile541Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00718 in 1,614,226 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 46 hom. )

Consequence

LRIT3
NM_198506.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

LRIT3 (HGNC:24783): (leucine rich repeat, Ig-like and transmembrane domains 3) This gene encodes a protein that has a fibronectin type III domain and a C-terminal transmembrane domain, as well as a leucine-rich repeat domain and immunoglobulin-like domain near the N-terminus. The encoded protein may regulate fibroblast growth factor receptors and affect the modification of these receptors, which are glycosylated differently in the Golgi and endoplasmic reticulum. Mutations in this gene are associated with congenital stationary night blindness, type 1F. [provided by RefSeq, May 2013]

LRIT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043292046).

BP6

Variant 4-109870370-A-G is Benign according to our data. Variant chr4-109870370-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 197396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-109870370-A-G is described in Lovd as [Benign]. Variant chr4-109870370-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIT3	NM_198506.5 linkuse as main transcript	c.1621A>G	p.Ile541Val	missense_variant	4/4	ENST00000594814.6	NP_940908.3	Q3SXY7-1
LRIT3	XM_017008167.2 linkuse as main transcript	c.1072A>G	p.Ile358Val	missense_variant	3/3		XP_016863656.1	A0A0A0MR64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIT3	ENST00000594814.6 linkuse as main transcript	c.1621A>G	p.Ile541Val	missense_variant	4/4	5	NM_198506.5	ENSP00000469759.1		Q3SXY7-1
LRIT3	ENST00000327908.3 linkuse as main transcript	c.1072A>G	p.Ile358Val	missense_variant	4/4	2		ENSP00000328222.3		A0A0A0MR64

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

703

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00766

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00509

AC:

1279

AN:

251140

Hom.:

AF XY:

0.00540

AC XY:

733

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00874

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00806

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00745

AC:

10891

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5404

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00968

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00246

Gnomad4 FIN exome

AF:

0.00417

Gnomad4 NFE exome

AF:

0.00862

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.00461

AC:

702

AN:

152348

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00766

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.00440

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00521

AC:

632

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00705

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	LRIT3: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 15, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 30, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0066

T;.

Eigen

Benign

0.0066

Eigen_PC

Benign

0.0019

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.49

.;N

REVEL

Benign

0.14

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.021

D;D

Vest4

0.12

MVP

0.15

MPC

0.14

ClinPred

0.033

GERP RS

2.6

Varity_R

0.069

gMVP

0.58

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