rs939421

Variant names:

• chr3-46534591-C-T
• rs939421
• NM_024512.5:c.491-1682G>A

Variant summary

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

The NM_024512.5(LRRC2):​c.491-1682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,820 control chromosomes in the GnomAD database, including 33,652 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 0.66 (33652 hom., cov: 30)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 14 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.491-1682G>A		intron_variant	Intron 4 of 8	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.491-1682G>A		intron_variant	Intron 4 of 8	1	NM_024512.5	ENSP00000379241.3
LRRC2	ENST00000296144.3	c.491-1682G>A		intron_variant	Intron 4 of 8	1		ENSP00000296144.3
LRRC2	ENST00000682605.1	c.491-1682G>A		intron_variant	Intron 4 of 8			ENSP00000507018.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99857 AN: 151702 Hom.: 33647 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.658 AC: 99895 AN: 151820 Hom.: 33652 Cov.: 30 AF XY: 0.655 AC XY: 48551 AN XY: 74160

African (AFR) AF: 0.589 AC: 24393 AN: 41388

American (AMR) AF: 0.573 AC: 8728 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2281 AN: 3466

East Asian (EAS) AF: 0.318 AC: 1646 AN: 5168

South Asian (SAS) AF: 0.685 AC: 3301 AN: 4818

European-Finnish (FIN) AF: 0.735 AC: 7723 AN: 10514

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49415 AN: 67918

Other (OTH) AF: 0.688 AC: 1454 AN: 2112

Alfa AF: 0.703 Hom.: 133223

Bravo AF: 0.643

Asia WGS AF: 0.497 AC: 1729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.12
PhyloP100		-0.92
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: rs939421; hg19: chr3-46576081;