11-72094686-T-TGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_145309.6(LRRC51):c.289-256_289-255dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 722,600 control chromosomes in the GnomAD database, including 4,448 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1265 hom., cov: 30)
  • Exomes 𝑓: 0.088 (3183 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605

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 -10 ACMG points.

• BP6: Variant 11-72094686-T-TGA is Benign according to our data. Variant chr11-72094686-T-TGA is described in ClinVar as [Benign]. Clinvar id is 1258396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC51	NM_145309.6	c.289-256_289-255dup		intron_variant		ENST00000289488.8
LRTOMT	NM_001145309.4	c.-115-256_-115-255dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC51	ENST00000289488.8	c.289-256_289-255dup		intron_variant		1	NM_145309.6	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17284 AN: 152030 Hom.: 1264 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.0881 AC: 50229 AN: 570452 Hom.: 3183 Cov.: 6 AF XY: 0.0904 AC XY: 27816 AN XY: 307572

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0895

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0544

Gnomad4 OTH exome AF: 0.0883

GnomAD4 genome AF: 0.114 AC: 17312 AN: 152148 Hom.: 1265 Cov.: 30 AF XY: 0.119 AC XY: 8825 AN XY: 74380

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0836 Hom.: 93

Bravo AF: 0.121

Asia WGS AF: 0.177 AC: 617 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

Jan 28, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34329029; hg19: chr11-71805732;