rs4698798

Variant names:

• chr4-109871473-A-G
• rs4698798
• NM_198506.5:c.*684A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296171 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LRIT3	NM_198506.5	c.*684A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000594814.6	NP_940908.3
LRIT3	XM_017008167.2	c.*684A>G		3_prime_UTR_variant	Exon 3 of 3		XP_016863656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIT3	ENST00000594814.6	c.*684A>G		3_prime_UTR_variant	Exon 4 of 4	5	NM_198506.5	ENSP00000469759.1
LRIT3	ENST00000327908.3	c.*684A>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000328222.3
ENSG00000296171	ENST00000737086.1	n.175-12954T>C		intron_variant	Intron 2 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.923 AC: 38370 AN: 41550

American (AMR) AF: 0.784 AC: 12005 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2649 AN: 3470

East Asian (EAS) AF: 0.658 AC: 3412 AN: 5184

South Asian (SAS) AF: 0.705 AC: 3399 AN: 4820

European-Finnish (FIN) AF: 0.709 AC: 7492 AN: 10568

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53361 AN: 67988

Other (OTH) AF: 0.791 AC: 1669 AN: 2110

Alfa AF: 0.794 Hom.: 21122

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4698798; hg19: chr4-110792629;