rs11919651

chr3-46552416-A-C

Variant summary

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

The NM_024512.5(LRRC2):c.-19-806T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 151,196 control chromosomes in the GnomAD database, including 981 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 0.10 (981 hom., cov: 31)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC2	NM_024512.5	c.-19-806T>G		intron_variant		ENST00000395905.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC2	ENST00000395905.8	c.-19-806T>G		intron_variant		1	NM_024512.5	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15655 AN: 151112 Hom.: 983 Cov.: 31

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.103 AC: 15647 AN: 151196 Hom.: 981 Cov.: 31 AF XY: 0.101 AC XY: 7468 AN XY: 73798

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.114

Alfa AF: 0.137 Hom.: 1506

Bravo AF: 0.100

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.59
Dann	Benign	0.50

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: rs11919651; hg19: chr3-46593906;