chr11-72088622-A-C

Variant names:

• chr11-72088622-A-C
• rs670802
• NM_145309.6:c.-56+242A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145309.6(LRRC51):​c.-56+242A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 570,294 control chromosomes in the GnomAD database, including 235,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (60160 hom., cov: 31)
  • Exomes 𝑓: 0.91 (174840 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240
• Publications: 4 publications found

Genes affected

LRRC51 (HGNC:55526): (leucine rich repeat containing 51) This gene belongs to the leucine-rich repeat containing family. The encoded protein contains a transmembrane domain and two leucine-rich repeat domains. Unlike in mouse and other mammals, readthrough transcription is observed in primates between this gene and the adjacent transmembrane O-methyltransferase (Tomt) gene. Previously, this locus was annotated as a single gene representing the readthrough transcripts as well as the two different transcript species that encoded different proteins. It has since been split into three genes, including the two stand-alone genes and a third gene representing the readthrough transcription. [provided by RefSeq, Feb 2022]

LRTOMT (HGNC:25033): (leucine rich transmembrane and O-methyltransferase domain containing) This locus represents naturally occurring readthrough transcription between the neighboring LRRC51 (leucine-rich repeat containing 51) and TOMT (transmembrane O-methyltransferase) genes on chromosome 11. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. Multiple reports implicate mutations in this gene in nonsyndromic deafness.[provided by RefSeq, Feb 2021]

LAMTOR1 (HGNC:26068): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 1) Enables GTPase binding activity. Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cholesterol homeostasis; positive regulation of TOR signaling; and regulation of cholesterol transport. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-72088622-A-C is Benign according to our data. Variant chr11-72088622-A-C is described in ClinVar as [Benign]. Clinvar id is 1251059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.-56+242A>C		intron_variant	Intron 2 of 5	ENST00000289488.8	NP_660352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.-56+242A>C		intron_variant	Intron 2 of 5	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-321-4874A>C		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134898 AN: 152020 Hom.: 60128 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.906

GnomAD4 exome AF: 0.912 AC: 381563 AN: 418156 Hom.: 174840 Cov.: 0 AF XY: 0.910 AC XY: 200092 AN XY: 219948

African (AFR) AF: 0.823 AC: 9699 AN: 11784

American (AMR) AF: 0.846 AC: 14312 AN: 16912

Ashkenazi Jewish (ASJ) AF: 0.911 AC: 11808 AN: 12964

East Asian (EAS) AF: 0.779 AC: 22848 AN: 29338

South Asian (SAS) AF: 0.844 AC: 34699 AN: 41090

European-Finnish (FIN) AF: 0.931 AC: 25336 AN: 27202

Middle Eastern (MID) AF: 0.917 AC: 1697 AN: 1850

European-Non Finnish (NFE) AF: 0.946 AC: 238861 AN: 252600

Other (OTH) AF: 0.913 AC: 22303 AN: 24416

GnomAD4 genome AF: 0.887 AC: 134988 AN: 152138 Hom.: 60160 Cov.: 31 AF XY: 0.882 AC XY: 65610 AN XY: 74362

African (AFR) AF: 0.818 AC: 33954 AN: 41488

American (AMR) AF: 0.829 AC: 12663 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3160 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3958 AN: 5142

South Asian (SAS) AF: 0.839 AC: 4041 AN: 4816

European-Finnish (FIN) AF: 0.932 AC: 9884 AN: 10604

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64284 AN: 68012

Other (OTH) AF: 0.908 AC: 1919 AN: 2114

Alfa AF: 0.900 Hom.: 3288

Bravo AF: 0.880

Asia WGS AF: 0.823 AC: 2859 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.63
PhyloP100		0.024
PromoterAI		0.035	Neutral
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: rs670802; hg19: chr11-71799668;