rs794727660

chr4-109869931-ATCT-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_198506.5(LRIT3):c.1187_1189del(p.Ser396del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,613,796 control chromosomes in the GnomAD database, including 1,130 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (79 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1051 hom.)
• Consequence: LRIT3 NM_198506.5 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.736

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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_198506.5
• BP6: Variant 4-109869931-ATCT-A is Benign according to our data. Variant chr4-109869931-ATCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 197394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0271 (4120/151978) while in subpopulation NFE AF= 0.0391 (2656/67916). AF 95% confidence interval is 0.0379. There are 79 homozygotes in gnomad4. There are 1962 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIT3	NM_198506.5	c.1187_1189del	p.Ser396del	inframe_deletion	4/4	ENST00000594814.6
LRIT3	XM_017008167.2	c.638_640del	p.Ser213del	inframe_deletion	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIT3	ENST00000594814.6	c.1187_1189del	p.Ser396del	inframe_deletion	4/4	5	NM_198506.5	P1
LRIT3	ENST00000327908.3	c.638_640del	p.Ser213del	inframe_deletion	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4121 AN: 151860 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00437

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0269 AC: 6747 AN: 250848 Hom.: 120 AF XY: 0.0277 AC XY: 3759 AN XY: 135688

Gnomad AFR exome AF: 0.00757

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.0511

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00800

Gnomad FIN exome AF: 0.0395

Gnomad NFE exome AF: 0.0378

Gnomad OTH exome AF: 0.0289

GnomAD4 exome AF: 0.0365 AC: 53295 AN: 1461818 Hom.: 1051 AF XY: 0.0359 AC XY: 26098 AN XY: 727204

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.0167

Gnomad4 ASJ exome AF: 0.0510

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00851

Gnomad4 FIN exome AF: 0.0391

Gnomad4 NFE exome AF: 0.0414

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0271 AC: 4120 AN: 151978 Hom.: 79 Cov.: 32 AF XY: 0.0264 AC XY: 1962 AN XY: 74304

Gnomad4 AFR AF: 0.00779

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0586

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00438

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0391

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0339 Hom.: 12

Bravo AF: 0.0257

EpiCase AF: 0.0426

EpiControl AF: 0.0425

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 17, 2014

- -

Congenital Stationary Night Blindness, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs794727660; hg19: chr4-110791087;