rs673478

Positions:

• chr11-72088058-G-A
• chr11-72088058-G-C
• chr11-72088058-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145309.6(LRRC51):​c.-139-239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,144 control chromosomes in the GnomAD database, including 60,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60475 hom., cov: 30)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

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:):

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-72088058-G-A is Benign according to our data. Variant chr11-72088058-G-A is described in ClinVar as [Benign]. Clinvar id is 1246309.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/exons	MANE	Protein	UniProt
LRRC51	NM_145309.6	c.-139-239G>A		intron_variant		ENST00000289488.8	NP_660352.1
LRTOMT	NM_001145309.4	c.-542-239G>A		intron_variant			NP_001138781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC51	ENST00000289488.8	c.-139-239G>A		intron_variant		1	NM_145309.6	ENSP00000289488	P1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135290 AN: 152026 Hom.: 60442 Cov.: 30

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.905

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135381 AN: 152144 Hom.: 60475 Cov.: 30 AF XY: 0.885 AC XY: 65834 AN XY: 74392

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.907

Alfa AF: 0.913 Hom.: 7877

Bravo AF: 0.882

Asia WGS AF: 0.823 AC: 2860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.7
DANN	Benign	0.20

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: rs673478; hg19: chr11-71799104;