rs3018301

Positions:

• chr11-72081025-A-G
• chr11-72081025-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145309.6(LRRC51):​c.-140+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,732 control chromosomes in the GnomAD database, including 52,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (51953 hom., cov: 32)
  • Exomes 𝑓: 0.91 (248 hom.)
• Consequence: LRRC51 NM_145309.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC51	NM_145309.6	c.-140+140A>G		intron_variant		ENST00000289488.8
LRTOMT	NM_001145309.4	c.-543+140A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC51	ENST00000289488.8	c.-140+140A>G		intron_variant		1	NM_145309.6	P1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123087 AN: 152034 Hom.: 51951 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.854

GnomAD4 exome AF: 0.912 AC: 529 AN: 580 Hom.: 248 AF XY: 0.897 AC XY: 357 AN XY: 398

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.611

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.942

Gnomad4 NFE exome AF: 0.933

Gnomad4 OTH exome AF: 0.942

GnomAD4 genome AF: 0.809 AC: 123118 AN: 152152 Hom.: 51953 Cov.: 32 AF XY: 0.808 AC XY: 60110 AN XY: 74378

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.857

Alfa AF: 0.855 Hom.: 10912

Bravo AF: 0.791

Asia WGS AF: 0.799 AC: 2776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.68

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: rs3018301; hg19: chr11-71792071; COSMIC: COSV56193056; COSMIC: COSV56193056;