Variant 4-109848188-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198506.5(LRIT3):c.-14C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00799 in 1,215,956 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 408 hom. )

Consequence

LRIT3
NM_198506.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.841

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:

RRH (HGNC:10450): (retinal pigment epithelium-derived rhodopsin homolog) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes opsin 5 and retinal G protein coupled receptor. [provided by RefSeq, Jul 2008]

RRH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-109848188-C-G is Benign according to our data. Variant chr4-109848188-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 347179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIT3	NM_198506.5 linkuse as main transcript	c.-14C>G		5_prime_UTR_variant	1/4	ENST00000594814.6	NP_940908.3
LRIT3	XM_017008168.2 linkuse as main transcript	c.-14C>G		5_prime_UTR_variant	1/3		XP_016863657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIT3	ENST00000594814.6 linkuse as main transcript	c.-14C>G		5_prime_UTR_variant	1/4	5	NM_198506.5	ENSP00000469759	P1	Q3SXY7-1
RRH	ENST00000652276.1 linkuse as main transcript	c.*3991C>G		3_prime_UTR_variant	4/4			ENSP00000498977

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1636

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00503

AC:

AN:

6158

Hom.:

AF XY:

0.00439

AC XY:

AN XY:

2960

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.167

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.00760

AC:

8083

AN:

1063704

Hom.:

408

Cov.:

AF XY:

0.00786

AC XY:

3952

AN XY:

502862

show subpopulations

Gnomad4 AFR exome

AF:

0.000973

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.000701

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0107

AC:

1636

AN:

152252

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1052

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0263

Gnomad4 NFE

AF:

0.00176

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00719

Asia WGS

AF:

0.109

AC:

376

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital Stationary Night Blindness, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.1

DANN

Benign

0.60

Splicing

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