chr3-46547323-C-A

Variant names:

• chr3-46547323-C-A
• rs9846026
• NM_024512.5:c.126-2070G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024512.5(LRRC2):​c.126-2070G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,094 control chromosomes in the GnomAD database, including 573 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 0.081 (573 hom., cov: 31)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 5 publications found

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]

LRRC2-AS1 (HGNC:15571): (LRRC2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.126-2070G>T		intron_variant	Intron 2 of 8	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.126-2070G>T		intron_variant	Intron 2 of 8	1	NM_024512.5	ENSP00000379241.3

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12224 AN: 151976 Hom.: 570 Cov.: 31

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0696

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

GnomAD4 genome AF: 0.0805 AC: 12248 AN: 152094 Hom.: 573 Cov.: 31 AF XY: 0.0851 AC XY: 6326 AN XY: 74344

African (AFR) AF: 0.0699 AC: 2901 AN: 41494

American (AMR) AF: 0.0387 AC: 592 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3468

East Asian (EAS) AF: 0.0921 AC: 476 AN: 5170

South Asian (SAS) AF: 0.169 AC: 814 AN: 4808

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10554

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5360 AN: 67990

Other (OTH) AF: 0.0693 AC: 146 AN: 2106

Alfa AF: 0.0813 Hom.: 66

Bravo AF: 0.0710

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.22
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9846026; hg19: chr3-46588813;