Genetic Variant LRRC27:p.Arg195Cys (chr10-132348013-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_030626.3(LRRC27):c.583C>T(p.Arg195Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,611,388 control chromosomes in the GnomAD database, including 34,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R195H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.15 ( 2187 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32565 hom. )

Consequence

LRRC27
NM_030626.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

Publications

28 publications found

Variant links:

Genes affected

LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

LRRC27 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=0.005176842).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC27	NM_030626.3 link	c.583C>T	p.Arg195Cys	missense_variant	Exon 6 of 11	ENST00000368614.8	NP_085129.1	Q9C0I9-1A0A140VJN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC27	ENST00000368614.8 link	c.583C>T	p.Arg195Cys	missense_variant	Exon 6 of 11	1	NM_030626.3	ENSP00000357603.3		Q9C0I9-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23175

AN:

152086

Hom.:

2190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0718

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.149

AC:

37375

AN:

250450

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.0980

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.000382

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.201

AC:

292912

AN:

1459184

Hom.:

32565

Cov.:

AF XY:

0.197

AC XY:

143072

AN XY:

725818

show subpopulations

African (AFR)

AF:

0.0681

AC:

2270

AN:

33356

American (AMR)

AF:

0.102

AC:

4551

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5362

AN:

26040

East Asian (EAS)

AF:

0.000378

AC:

AN:

39682

South Asian (SAS)

AF:

0.0691

AC:

5952

AN:

86168

European-Finnish (FIN)

AF:

0.112

AC:

5953

AN:

53230

Middle Eastern (MID)

AF:

0.182

AC:

887

AN:

4876

European-Non Finnish (NFE)

AF:

0.231

AC:

256926

AN:

1111104

Other (OTH)

AF:

0.183

AC:

10996

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11985

23970

35956

47941

59926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8566

17132

25698

34264

42830

<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:

0.152

AC:

23168

AN:

152204

Hom.:

2187

Cov.:

AF XY:

0.144

AC XY:

10688

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0718

AC:

2983

AN:

41538

American (AMR)

AF:

0.143

AC:

2180

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

754

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5182

South Asian (SAS)

AF:

0.0609

AC:

293

AN:

4810

European-Finnish (FIN)

AF:

0.100

AC:

1064

AN:

10606

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15313

AN:

67986

Other (OTH)

AF:

0.153

AC:

324

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

987

1975

2962

3950

4937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.194

Hom.:

12283

Bravo

AF:

0.153

TwinsUK

AF:

0.231

AC:

856

ALSPAC

AF:

0.232

AC:

895

ESP6500AA

AF:

0.0685

AC:

302

ESP6500EA

AF:

0.226

AC:

1941

ExAC

AF:

0.151

AC:

18331

Asia WGS

AF:

0.0320

AC:

114

AN:

3478

EpiCase

AF:

0.228

EpiControl

AF:

0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.1

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.029

.;.;T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.64

T;T;.;T;T

MetaRNN

Benign

0.0052

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;N;N;.

PhyloP100

-0.12

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

N;.;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.10

T;.;T;T;T

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.0040

B;B;B;B;B

Vest4

0.051

MPC

0.081

ClinPred

0.0018

GERP RS

-0.65

Varity_R

0.057

gMVP

0.28

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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