rs12272086

Positions:

• chr11-72104998-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001145309.4(LRTOMT):​c.69G>C​(p.Leu23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,550,840 control chromosomes in the GnomAD database, including 2,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (652 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1938 hom.)
• Consequence: LRTOMT NM_001145309.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.295

Genes affected

LRTOMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-72104998-G-C is Benign according to our data. Variant chr11-72104998-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 44042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.295 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRTOMT	NM_001145309.4	c.69G>C	p.Leu23=	synonymous_variant	6/9		NP_001138781.1
LRTOMT	NM_001145308.5	c.69G>C	p.Leu23=	synonymous_variant	4/7		NP_001138780.1
LRTOMT	NM_001145310.4	c.69G>C	p.Leu23=	synonymous_variant	6/9		NP_001138782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11125 AN: 152068 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0525

GnomAD3 exomes AF: 0.0681 AC: 10519 AN: 154352 Hom.: 604 AF XY: 0.0674 AC XY: 5511 AN XY: 81818

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.0426

Gnomad EAS exome AF: 0.163

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0349

Gnomad NFE exome AF: 0.0215

Gnomad OTH exome AF: 0.0490

GnomAD4 exome AF: 0.0357 AC: 49959 AN: 1398654 Hom.: 1938 Cov.: 31 AF XY: 0.0374 AC XY: 25770 AN XY: 689802

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0414

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0203

Gnomad4 OTH exome AF: 0.0456

GnomAD4 genome AF: 0.0733 AC: 11149 AN: 152186 Hom.: 652 Cov.: 32 AF XY: 0.0774 AC XY: 5755 AN XY: 74398

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0332 Hom.: 44

Bravo AF: 0.0800

Asia WGS AF: 0.120 AC: 420 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Leu23Leu in Exon 04 of LRTOMT: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 12.8% (90/702) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12272086). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hearing loss, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Uncertain	0.98

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: rs12272086; hg19: chr11-71816044; COSMIC: COSV53825503; COSMIC: COSV53825503;