3-46528231-G-T

Position:

• chr3-46528231-G-T

Variant summary

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

The NM_024512.5(LRRC2):​c.774-650C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,740 control chromosomes in the GnomAD database, including 20,834 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 0.51 (20834 hom., cov: 30)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.774-650C>A		intron_variant		ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.774-650C>A		intron_variant		1	NM_024512.5	ENSP00000379241	P1
LRRC2	ENST00000296144.3	c.774-650C>A		intron_variant		1		ENSP00000296144	P1
LRRC2	ENST00000682605.1	c.774-650C>A		intron_variant				ENSP00000507018	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77711 AN: 151622 Hom.: 20828 Cov.: 30

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.512 AC: 77743 AN: 151740 Hom.: 20834 Cov.: 30 AF XY: 0.521 AC XY: 38644 AN XY: 74120

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.496

Alfa AF: 0.555 Hom.: 53558

Bravo AF: 0.492

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.43

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: rs6791703; hg19: chr3-46569721;