rs939421

chr3-46534591-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
LRRC2	NM_024512.5	c.491-1682G>A		intron_variant		ENST00000395905.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC2	ENST00000395905.8	c.491-1682G>A		intron_variant		1	NM_024512.5	P1
LRRC2	ENST00000296144.3	c.491-1682G>A		intron_variant		1		P1
LRRC2	ENST00000682605.1	c.491-1682G>A		intron_variant				P1

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

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.688

Alfa AF: 0.715 Hom.: 60648

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

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: rs939421; hg19: chr3-46576081;