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

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

Variant links:

Genes affected

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

LRRC36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Q1X8D7-1

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		Q1X8D7-1

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

GnomAD3 exomes

AF:

0.0793

AC:

19851

AN:

250348

Hom.:

2588

AF XY:

0.0725

AC XY:

9816

AN XY:

135420

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 SAS exome

AF:

0.0821

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

Gnomad4 AFR exome

AF:

0.536

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.0663

Gnomad4 EAS exome

AF:

0.00161

Gnomad4 SAS exome

AF:

0.0777

Gnomad4 FIN exome

AF:

0.0419

Gnomad4 NFE exome

AF:

0.0437

Gnomad4 OTH exome

AF:

0.0827

GnomAD4 genome

AF:

0.178

AC:

26880

AN:

150984

Hom.:

5712

Cov.:

AF XY:

0.173

AC XY:

12753

AN XY:

73632

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.0939

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.00409

Gnomad4 SAS

AF:

0.0718

Gnomad4 FIN

AF:

0.0377

Gnomad4 NFE

AF:

0.0437

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.0638

Hom.:

1825

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over