4-109868706-T-C

Variant names:

• chr4-109868706-T-C
• rs10488880
• NM_198506.5:c.895+760T>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_198506.5(LRIT3):c.895+760T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRIT3 NM_198506.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 0 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296171 (HGNC:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_198506.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LRIT3 NM_198506.5	MANE Select	c.895+760T>C	intron	Intron 3 of 3	Prot: NP_940908.3 UniProt:

LRIT3 NM_198506.5

MANE Select

HGVSc / HGVSpc.895+760T>C

Exon rankIntron 3 of 3

intron

Prot: NP_940908.3UniProt: Q3SXY7-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LRIT3 ENST00000594814.6	TSL:5MANE Select	c.895+760T>C	intron	Intron 3 of 3	Prot: ENSP00000469759.1 UniProt:
	LRIT3 ENST00000876618.1		c.895+760T>C	intron	Intron 4 of 4	Prot: ENSP00000546677.1 UniProt:
	LRIT3 ENST00000327908.3	TSL:2	c.346+760T>C	intron	Intron 3 of 3	Prot: ENSP00000328222.3 UniProt:

LRIT3 ENST00000594814.6

TSL:5MANE Select

HGVSc / HGVSpc.895+760T>C

Exon rankIntron 3 of 3

intron

Prot: ENSP00000469759.1UniProt: Q3SXY7-1

LRIT3 ENST00000876618.1

HGVSc / HGVSpc.895+760T>C

Exon rankIntron 4 of 4

intron

Prot: ENSP00000546677.1UniProt: Q3SXY7-1

LRIT3 ENST00000327908.3

TSL:2

HGVSc / HGVSpc.346+760T>C

Exon rankIntron 3 of 3

intron

Prot: ENSP00000328222.3UniProt: A0A0A0MR64

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:12	AN:24268	Cov:

Showing 3 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.4
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.70
GPN-Star LLR	N/A	0.40
GPN-Star score	N/A	-0.40
PhyloP100	Benign	-0.36

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs10488880;

hg19: chr4-110789862;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar