rs11200928

chr10-84224967-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001017924.5(LRIT2):c.258C>T(p.Leu86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,613,762 control chromosomes in the GnomAD database, including 41,905 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 0.19 (3127 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38778 hom.)
• Consequence: LRIT2 NM_001017924.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

Genes affected

LRIT2 (HGNC:23443): (leucine rich repeat, Ig-like and transmembrane domains 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.108 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRIT2	NM_001017924.5	c.258C>T	p.Leu86=	synonymous_variant	2/3	ENST00000372113.7
LRIT2	NM_001284223.1	c.258C>T	p.Leu86=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRIT2	ENST00000372113.7	c.258C>T	p.Leu86=	synonymous_variant	2/3	1	NM_001017924.5	P2
LRIT2	ENST00000538192.5	c.258C>T	p.Leu86=	synonymous_variant	2/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28100 AN: 151966 Hom.: 3113 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.217 AC: 54460 AN: 251454 Hom.: 6376 AF XY: 0.217 AC XY: 29501 AN XY: 135900

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.330

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.226 AC: 330649 AN: 1461678 Hom.: 38778 Cov.: 35 AF XY: 0.226 AC XY: 164155 AN XY: 727160

Gnomad4 AFR exome AF: 0.0780

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.185 AC: 28144 AN: 152084 Hom.: 3127 Cov.: 32 AF XY: 0.183 AC XY: 13600 AN XY: 74328

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.216

Alfa AF: 0.210 Hom.: 2667

Bravo AF: 0.194

Asia WGS AF: 0.273 AC: 946 AN: 3478

EpiCase AF: 0.224

EpiControl AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	6.3
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11200928; hg19: chr10-85984723; COSMIC: COSV64518744;