3-46532867-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024512.5(LRRC2):c.533A>C(p.Tyr178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,614,010 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

LRRC2
NM_024512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0300

Publications

6 publications found

Variant links:

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]

LRRC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008144259).

BP6

Variant 3-46532867-T-G is Benign according to our data. Variant chr3-46532867-T-G is described in ClinVar as [Benign]. Clinvar id is 731673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000545 (797/1461668) while in subpopulation AFR AF = 0.0161 (540/33468). AF 95% confidence interval is 0.015. There are 1 homozygotes in GnomAdExome4. There are 359 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5 link	c.533A>C	p.Tyr178Ser	missense_variant	Exon 5 of 9	ENST00000395905.8	NP_078788.2	Q9BYS8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRC2	ENST00000395905.8 link	c.533A>C	p.Tyr178Ser	missense_variant	Exon 5 of 9	1	NM_024512.5	ENSP00000379241.3	Q9BYS8
LRRC2	ENST00000296144.3 link	c.533A>C	p.Tyr178Ser	missense_variant	Exon 5 of 9	1		ENSP00000296144.3	Q9BYS8
LRRC2	ENST00000682605.1 link	c.533A>C	p.Tyr178Ser	missense_variant	Exon 5 of 9			ENSP00000507018.1	Q9BYS8

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00128

AC:

321

AN:

251276

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000545

AC:

797

AN:

1461668

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.0161

AC:

540

AN:

33468

American (AMR)

AF:

0.00132

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000782

AC:

AN:

1111874

Other (OTH)

AF:

0.00154

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00451

AC:

687

AN:

152342

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

343

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0155

AC:

643

AN:

41582

American (AMR)

AF:

0.00170

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00524

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00147

AC:

179

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.000025

T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.46

.;T

MetaRNN

Benign

0.0081

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.60

N;N

PhyloP100

-0.030

PrimateAI

Benign

0.28

PROVEAN

Benign

0.81

N;N

REVEL

Benign

0.037

Sift

Uncertain

0.024

D;D

Sift4G

Benign

0.24

T;T

Polyphen

0.022

B;B

Vest4

0.17

MVP

0.095

MPC

0.38

ClinPred

0.042

GERP RS

-1.1

Varity_R

0.093

gMVP

0.29

Mutation Taster

=98/2

polymorphism

(source)

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

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3-46532867-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over