rs114400071

Variant names:

• chr11-72093387-A-G
• rs114400071
• NM_145309.6:c.83-109A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-72093387-A-G
• chr11-72093387-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145309.6(LRRC51):​c.83-109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,080,268 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (13 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91
• Publications: 0 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=-0.8).
• BP6: Variant 11-72093387-A-G is Benign according to our data. Variant chr11-72093387-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1205440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00898 (1368/152314) while in subpopulation AFR AF = 0.0314 (1306/41570). AF 95% confidence interval is 0.03. There are 15 homozygotes in GnomAd4. There are 621 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.83-109A>G		intron_variant	Intron 3 of 5	ENST00000289488.8	NP_660352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.83-109A>G		intron_variant	Intron 3 of 5	1	NM_145309.6	ENSP00000289488.2
LRTOMT	ENST00000307198.11	c.-321-109A>G		intron_variant	Intron 1 of 6	2		ENSP00000305742.7

Frequencies

GnomAD3 genomes AF: 0.00897 AC: 1365 AN: 152196 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000949 AC: 881 AN: 927954 Hom.: 13 AF XY: 0.000827 AC XY: 394 AN XY: 476604

African (AFR) AF: 0.0321 AC: 716 AN: 22294

American (AMR) AF: 0.00154 AC: 54 AN: 35084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22252

East Asian (EAS) AF: 0.00 AC: 0 AN: 33548

South Asian (SAS) AF: 0.0000289 AC: 2 AN: 69186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48248

Middle Eastern (MID) AF: 0.000316 AC: 1 AN: 3162

European-Non Finnish (NFE) AF: 0.0000169 AC: 11 AN: 651878

Other (OTH) AF: 0.00229 AC: 97 AN: 42302

GnomAD4 genome AF: 0.00898 AC: 1368 AN: 152314 Hom.: 15 Cov.: 32 AF XY: 0.00834 AC XY: 621 AN XY: 74494

African (AFR) AF: 0.0314 AC: 1306 AN: 41570

American (AMR) AF: 0.00320 AC: 49 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00563 Hom.: 0

Bravo AF: 0.0104

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2018

GeneDx

Significance: Likely 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	-0.80
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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: rs114400071; hg19: chr11-71804433;