11-72088919-T-C

Position:

• chr11-72088919-T-C

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.-55-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,291,252 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (87 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115

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=-0.8).
• BP6: Variant 11-72088919-T-C is Benign according to our data. Variant chr11-72088919-T-C is described in ClinVar as [Benign]. Clinvar id is 1247784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC51	NM_145309.6	c.-55-110T>C		intron_variant		ENST00000289488.8
LRTOMT	NM_001145309.4	c.-458-110T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC51	ENST00000289488.8	c.-55-110T>C		intron_variant		1	NM_145309.6	P1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3281 AN: 152072 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00229 AC: 2613 AN: 1139062 Hom.: 87 Cov.: 14 AF XY: 0.00201 AC XY: 1150 AN XY: 572488

Gnomad4 AFR exome AF: 0.0787

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.0000909

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0000277

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.00539

GnomAD4 genome AF: 0.0216 AC: 3292 AN: 152190 Hom.: 124 Cov.: 32 AF XY: 0.0210 AC XY: 1565 AN XY: 74400

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0137 Hom.: 10

Bravo AF: 0.0249

Asia WGS AF: 0.00491 AC: 17 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

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.60

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: rs78796585; hg19: chr11-71799965;