rs10488880

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-109868706-T-A
• chr4-109868706-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198506.5(LRIT3):​c.895+760T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 152,216 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (222 hom., 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIT3	NM_198506.5	c.895+760T>A		intron_variant	Intron 3 of 3	ENST00000594814.6	NP_940908.3
LRIT3	XM_017008167.2	c.346+760T>A		intron_variant	Intron 2 of 2		XP_016863656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIT3	ENST00000594814.6	c.895+760T>A		intron_variant	Intron 3 of 3	5	NM_198506.5	ENSP00000469759.1
LRIT3	ENST00000327908.3	c.346+760T>A		intron_variant	Intron 3 of 3	2		ENSP00000328222.3
ENSG00000296171	ENST00000737086.1	n.175-10187A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4580 AN: 152098 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0302 AC: 4597 AN: 152216 Hom.: 222 Cov.: 32 AF XY: 0.0295 AC XY: 2197 AN XY: 74448

African (AFR) AF: 0.100 AC: 4155 AN: 41516

American (AMR) AF: 0.0126 AC: 193 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68006

Other (OTH) AF: 0.0312 AC: 66 AN: 2114

Alfa AF: 0.00381 Hom.: 3

Bravo AF: 0.0330

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.95
DANN	Benign	0.58
PhyloP100		-0.36
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: rs10488880; hg19: chr4-110789862;