rs4698798

Positions:

• chr4-109871473-A-G
• chr4-109871473-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198506.5(LRIT3):​c.*684A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,200 control chromosomes in the GnomAD database, including 50,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50279 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LRIT3 NM_198506.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 4-109871473-A-G is Benign according to our data. Variant chr4-109871473-A-G is described in ClinVar as [Benign]. Clinvar id is 347206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIT3	NM_198506.5	c.*684A>G		3_prime_UTR_variant	4/4	ENST00000594814.6	NP_940908.3
LRIT3	XM_017008167.2	c.*684A>G		3_prime_UTR_variant	3/3		XP_016863656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIT3	ENST00000594814.6	c.*684A>G		3_prime_UTR_variant	4/4	5	NM_198506.5	ENSP00000469759	P1
LRIT3	ENST00000327908.3	c.*684A>G		3_prime_UTR_variant	4/4	2		ENSP00000328222

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123142 AN: 152082 Hom.: 50219 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.788

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.810 AC: 123257 AN: 152200 Hom.: 50279 Cov.: 32 AF XY: 0.804 AC XY: 59779 AN XY: 74394

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.791

Alfa AF: 0.802 Hom.: 13471

Bravo AF: 0.824

Asia WGS AF: 0.717 AC: 2491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital Stationary Night Blindness, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

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	-0.98
CADD	Benign	1.5
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs4698798; hg19: chr4-110792629;