rs1402152

Variant names:

• chr3-46532928-A-G
• rs1402152
• NM_024512.5:c.491-19T>C

Variant summary

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

The NM_024512.5(LRRC2):​c.491-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,610,596 control chromosomes in the GnomAD database, including 98,631 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.34 (8946 hom., cov: 32)
  • Exomes 𝑓: 0.35 (89685 hom.)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 17 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.491-19T>C		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.491-19T>C		intron_variant	Intron 4 of 8	1	NM_024512.5	ENSP00000379241.3
LRRC2	ENST00000296144.3	c.491-19T>C		intron_variant	Intron 4 of 8	1		ENSP00000296144.3
LRRC2	ENST00000682605.1	c.491-19T>C		intron_variant	Intron 4 of 8			ENSP00000507018.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51641 AN: 151948 Hom.: 8944 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.340

GnomAD2 exomes AF: 0.350 AC: 87402 AN: 249932 AF XY: 0.360

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.311

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.347 AC: 506218 AN: 1458530 Hom.: 89685 Cov.: 33 AF XY: 0.352 AC XY: 255202 AN XY: 725648

African (AFR) AF: 0.318 AC: 10585 AN: 33294

American (AMR) AF: 0.228 AC: 10113 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8141 AN: 26038

East Asian (EAS) AF: 0.281 AC: 11156 AN: 39636

South Asian (SAS) AF: 0.456 AC: 39169 AN: 85970

European-Finnish (FIN) AF: 0.462 AC: 24652 AN: 53370

Middle Eastern (MID) AF: 0.422 AC: 2412 AN: 5722

European-Non Finnish (NFE) AF: 0.342 AC: 379486 AN: 1109882

Other (OTH) AF: 0.340 AC: 20504 AN: 60228

GnomAD4 genome AF: 0.340 AC: 51678 AN: 152066 Hom.: 8946 Cov.: 32 AF XY: 0.346 AC XY: 25698 AN XY: 74310

African (AFR) AF: 0.322 AC: 13379 AN: 41498

American (AMR) AF: 0.259 AC: 3964 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1064 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1496 AN: 5160

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4818

European-Finnish (FIN) AF: 0.466 AC: 4915 AN: 10550

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23449 AN: 67972

Other (OTH) AF: 0.338 AC: 712 AN: 2104

Alfa AF: 0.340 Hom.: 7914

Bravo AF: 0.322

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.6
DANN	Benign	0.82
PhyloP100		0.49
BranchPoint Hunter		5.0
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: rs1402152; hg19: chr3-46574418; COSMIC: COSV56128719;