10-84232634-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015613.3(LRIT1):c.1165C>A(p.Pro389Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,613,418 control chromosomes in the GnomAD database, including 12,293 homozygotes. 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.

Frequency

Genomes: 𝑓 0.18 ( 5356 hom., cov: 32)

Exomes 𝑓: 0.059 ( 6937 hom. )

Consequence

LRIT1
NM_015613.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

17 publications found

Variant links:

Genes affected

LRIT1 (HGNC:23404): (leucine rich repeat, Ig-like and transmembrane domains 1) Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRIT1 links:

RGR (HGNC:9990): (retinal G protein coupled receptor) This gene encodes a putative retinal G-protein coupled receptor. The gene is a member of the opsin subfamily of the 7 transmembrane, G-protein coupled receptor 1 family. Like other opsins which bind retinaldehyde, it contains a conserved lysine residue in the seventh transmembrane domain. The protein acts as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. The reverse isomerization occurs with rhodopsin in retinal photoreceptor cells. The protein is exclusively expressed in tissue adjacent to retinal photoreceptor cells, the retinal pigment epithelium and Mueller cells. This gene may be associated with autosomal recessive and autosomal dominant retinitis pigmentosa (arRP and adRP, respectively). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

RGR Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 44
Inheritance: Unknown, SD, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

RGR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2184849E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIT1	NM_015613.3 link	c.1165C>A	p.Pro389Thr	missense_variant	Exon 4 of 4	ENST00000372105.4	NP_056428.1
LRIT1	XM_011539626.3 link	c.580C>A	p.Pro194Thr	missense_variant	Exon 3 of 3		XP_011537928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIT1	ENST00000372105.4 link	c.1165C>A	p.Pro389Thr	missense_variant	Exon 4 of 4	1	NM_015613.3	ENSP00000361177.3
RGR	ENST00000652073.1 link	c.-459+159G>T		intron_variant	Intron 2 of 7			ENSP00000498800.1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27240

AN:

152028

Hom.:

5344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.0831

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0406

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.101

AC:

25362

AN:

250728

AF XY:

0.0886

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0627

Gnomad EAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.0834

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0797

GnomAD4 exome

AF:

0.0593

AC:

86725

AN:

1461272

Hom.:

6937

Cov.:

AF XY:

0.0582

AC XY:

42321

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.509

AC:

17028

AN:

33458

American (AMR)

AF:

0.183

AC:

8163

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

1582

AN:

26130

East Asian (EAS)

AF:

0.0348

AC:

1380

AN:

39692

South Asian (SAS)

AF:

0.0846

AC:

7295

AN:

86248

European-Finnish (FIN)

AF:

0.0818

AC:

4368

AN:

53366

Middle Eastern (MID)

AF:

0.0637

AC:

367

AN:

5764

European-Non Finnish (NFE)

AF:

0.0375

AC:

41700

AN:

1111556

Other (OTH)

AF:

0.0802

AC:

4842

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4868

9737

14605

19474

24342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1882

3764

5646

7528

9410

<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:

0.179

AC:

27277

AN:

152146

Hom.:

5356

Cov.:

AF XY:

0.178

AC XY:

13215

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.488

AC:

20217

AN:

41460

American (AMR)

AF:

0.145

AC:

2209

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

218

AN:

3470

East Asian (EAS)

AF:

0.0432

AC:

224

AN:

5186

South Asian (SAS)

AF:

0.0919

AC:

443

AN:

4822

European-Finnish (FIN)

AF:

0.0831

AC:

881

AN:

10604

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0406

AC:

2763

AN:

68006

Other (OTH)

AF:

0.139

AC:

293

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

844

1689

2533

3378

4222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.0871

Hom.:

6002

Bravo

AF:

0.200

TwinsUK

AF:

0.0383

AC:

142

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.470

AC:

2073

ESP6500EA

AF:

0.0443

AC:

381

ExAC

AF:

0.104

AC:

12664

Asia WGS

AF:

0.0870

AC:

307

AN:

3478

EpiCase

AF:

0.0398

EpiControl

AF:

0.0390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.6

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.010

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.53

MetaRNN

Benign

0.00022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

-0.0030

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.045

Sift

Benign

0.47

Sift4G

Benign

0.12

Polyphen

0.036

Vest4

0.015

MPC

0.090

ClinPred

0.0029

GERP RS

2.8

Varity_R

0.048

gMVP

0.45

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over