dbSNP rs8052655: LRRC36:p.Gly509Ser (chr16-67375277-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018296.6(LRRC36):c.1525G>A(p.Gly509Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 1,611,768 control chromosomes in the GnomAD database, including 12,601 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 5712 hom., cov: 31)

Exomes 𝑓: 0.059 ( 6889 hom. )

Consequence

LRRC36
NM_018296.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

28 publications found

Variant links:

Genes affected

LRRC36 (HGNC:25615): (leucine rich repeat containing 36)

LRRC36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011099577).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC36	NM_018296.6 link	c.1525G>A	p.Gly509Ser	missense_variant	Exon 10 of 14	ENST00000329956.11	NP_060766.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC36	ENST00000329956.11 link	c.1525G>A	p.Gly509Ser	missense_variant	Exon 10 of 14	1	NM_018296.6	ENSP00000329943.6

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

26808

AN:

150874

Hom.:

5682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.0940

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.00408

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0437

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.0793

AC:

19851

AN:

250348

AF XY:

0.0725

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.0646

Gnomad EAS exome

AF:

0.00246

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0455

Gnomad OTH exome

AF:

0.0641

GnomAD4 exome

AF:

0.0585

AC:

85515

AN:

1460784

Hom.:

6889

Cov.:

AF XY:

0.0576

AC XY:

41895

AN XY:

726772

show subpopulations

African (AFR)

AF:

0.536

AC:

17896

AN:

33372

American (AMR)

AF:

0.0577

AC:

2579

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

1732

AN:

26124

East Asian (EAS)

AF:

0.00161

AC:

AN:

39696

South Asian (SAS)

AF:

0.0777

AC:

6696

AN:

86226

European-Finnish (FIN)

AF:

0.0419

AC:

2208

AN:

52734

Middle Eastern (MID)

AF:

0.137

AC:

790

AN:

5766

European-Non Finnish (NFE)

AF:

0.0437

AC:

48559

AN:

1111804

Other (OTH)

AF:

0.0827

AC:

4991

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

3884

7768

11653

15537

19421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2102

4204

6306

8408

10510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.178

AC:

26880

AN:

150984

Hom.:

5712

Cov.:

AF XY:

0.173

AC XY:

12753

AN XY:

73632

show subpopulations

African (AFR)

AF:

0.514

AC:

21130

AN:

41096

American (AMR)

AF:

0.0939

AC:

1422

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.0616

AC:

214

AN:

3472

East Asian (EAS)

AF:

0.00409

AC:

AN:

5136

South Asian (SAS)

AF:

0.0718

AC:

343

AN:

4776

European-Finnish (FIN)

AF:

0.0377

AC:

386

AN:

10242

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0437

AC:

2964

AN:

67812

Other (OTH)

AF:

0.142

AC:

298

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

769

1537

2306

3074

3843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0831

Hom.:

7490

Bravo

AF:

0.194

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0446

AC:

172

ESP6500AA

AF:

0.503

AC:

2213

ESP6500EA

AF:

0.0428

AC:

368

ExAC

AF:

0.0898

AC:

10897

Asia WGS

AF:

0.0740

AC:

259

AN:

3478

EpiCase

AF:

0.0462

EpiControl

AF:

0.0508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

L;.

PhyloP100

3.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.17

Sift

Benign

0.26

T;T

Sift4G

Uncertain

0.056

T;T

Polyphen

1.0

D;D

Vest4

0.16

MPC

0.82

ClinPred

0.017

GERP RS

5.7

Varity_R

0.12

gMVP

0.36

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over