rs35997283

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/22 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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

congenital stationary night blindness 1F
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LRIT3 links:

ENSG00000296171 (HGNC:):

ENSG00000296171 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 197396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198506.5. 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
	LRIT3	NM_198506.5	MANE Select	c.1621A>G	p.Ile541Val	missense	Exon 4 of 4	NP_940908.3	Q3SXY7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRIT3	ENST00000594814.6	TSL:5 MANE Select	c.1621A>G	p.Ile541Val	missense	Exon 4 of 4	ENSP00000469759.1	Q3SXY7-1
LRIT3	ENST00000876618.1		c.1621A>G	p.Ile541Val	missense	Exon 5 of 5	ENSP00000546677.1
LRIT3	ENST00000327908.3	TSL:2	c.1072A>G	p.Ile358Val	missense	Exon 4 of 4	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

GnomAD2 exomes

AF:

0.00509

AC:

1279

AN:

251140

AF XY:

0.00540

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 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

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.00268

AC:

120

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00968

AC:

253

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00246

AC:

212

AN:

86250

European-Finnish (FIN)

AF:

0.00417

AC:

223

AN:

53420

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00862

AC:

9587

AN:

1112006

Other (OTH)

AF:

0.00760

AC:

459

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

694

1388

2083

2777

3471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.00461

AC:

702

AN:

152348

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41586

American (AMR)

AF:

0.00281

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00254

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00766

AC:

521

AN:

68028

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00640

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0066

Eigen

Benign

0.0066

Eigen_PC

Benign

0.0019

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

M_CAP

Benign

0.0098

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.49

REVEL

Benign

0.14

Sift

Uncertain

0.014

Sift4G

Uncertain

0.021

Vest4

0.12

MVP

0.15

MPC

0.14

ClinPred

0.033

GERP RS

2.6

Varity_R

0.069

gMVP

0.58

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over