3-46526667-T-C

Position:

• chr3-46526667-T-C

Variant summary

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

The NM_024512.5(LRRC2):​c.929+759A>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 152,318 control chromosomes in the GnomAD database, including 1,186 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 (1186 hom., cov: 32)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.929+759A>G		intron_variant		ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.929+759A>G		intron_variant		1	NM_024512.5	ENSP00000379241	P1
LRRC2	ENST00000296144.3	c.929+759A>G		intron_variant		1		ENSP00000296144	P1
LRRC2	ENST00000682605.1	c.929+759A>G		intron_variant				ENSP00000507018	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15660 AN: 152202 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0942

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

GnomAD4 genome AF: 0.103 AC: 15696 AN: 152318 Hom.: 1186 Cov.: 32 AF XY: 0.106 AC XY: 7866 AN XY: 74478

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0732 Hom.: 150

Bravo AF: 0.111

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.94
DANN	Benign	0.48

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: rs1879328; hg19: chr3-46568157;