4-109848188-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.841

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
LRIT3	NM_198506.5	c.-14C>G		5_prime_UTR_variant	1/4	ENST00000594814.6
LRIT3	XM_017008168.2	c.-14C>G		5_prime_UTR_variant	1/3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1636 AN: 152134 Hom.: 79 Cov.: 32

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: 31 AN: 6158 Hom.: 4 AF XY: 0.00439 AC XY: 13 AN XY: 2960

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.: 20 AF XY: 0.00786 AC XY: 3952 AN XY: 502862

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.: 79 Cov.: 32 AF XY: 0.0141 AC XY: 1052 AN XY: 74438

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.: 3

Bravo AF: 0.00719

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

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

Other links and lift over

dbSNP: rs77613966; hg19: chr4-110769344;