Genetic Variant LRRC1:p.Ile193Val (chr6-53897294-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018214.5(LRRC1):c.577A>G(p.Ile193Val) variant causes a missense change. The variant allele was found at a frequency of 0.093 in 1,607,402 control chromosomes in the GnomAD database, including 9,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.089 ( 913 hom., cov: 32)

Exomes 𝑓: 0.093 ( 8222 hom. )

Consequence

LRRC1
NM_018214.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Publications

28 publications found

Variant links:

Genes affected

LRRC1 (HGNC:14307): (leucine rich repeat containing 1) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC1 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=0.0013781786).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC1	NM_018214.5 link	c.577A>G	p.Ile193Val	missense_variant	Exon 7 of 14	ENST00000370888.6	NP_060684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC1	ENST00000370888.6 link	c.577A>G	p.Ile193Val	missense_variant	Exon 7 of 14	1	NM_018214.5	ENSP00000359925.1
LRRC1	ENST00000487251.5 link	n.573A>G		non_coding_transcript_exon_variant	Exon 8 of 11	2		ENSP00000435217.1

Frequencies

GnomAD3 genomes

AF:

0.0886

AC:

13480

AN:

152090

Hom.:

905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.0769

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.120

AC:

29943

AN:

249814

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0841

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0935

AC:

136029

AN:

1455194

Hom.:

8222

Cov.:

AF XY:

0.0932

AC XY:

67504

AN XY:

724270

show subpopulations

African (AFR)

AF:

0.0197

AC:

657

AN:

33418

American (AMR)

AF:

0.262

AC:

11669

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3305

AN:

26064

East Asian (EAS)

AF:

0.257

AC:

10188

AN:

39600

South Asian (SAS)

AF:

0.0686

AC:

5899

AN:

85978

European-Finnish (FIN)

AF:

0.104

AC:

5474

AN:

52770

Middle Eastern (MID)

AF:

0.0799

AC:

454

AN:

5684

European-Non Finnish (NFE)

AF:

0.0836

AC:

92553

AN:

1106930

Other (OTH)

AF:

0.0969

AC:

5830

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4967

9934

14901

19868

24835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3480

6960

10440

13920

17400

<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:

0.0888

AC:

13509

AN:

152208

Hom.:

913

Cov.:

AF XY:

0.0923

AC XY:

6869

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0244

AC:

1014

AN:

41550

American (AMR)

AF:

0.201

AC:

3079

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3468

East Asian (EAS)

AF:

0.245

AC:

1266

AN:

5166

South Asian (SAS)

AF:

0.0772

AC:

372

AN:

4818

European-Finnish (FIN)

AF:

0.104

AC:

1105

AN:

10586

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0879

AC:

5975

AN:

68006

Other (OTH)

AF:

0.106

AC:

224

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

586

1172

1758

2344

2930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0905

Hom.:

2321

Bravo

AF:

0.0958

TwinsUK

AF:

0.0868

AC:

322

ALSPAC

AF:

0.0784

AC:

302

ESP6500AA

AF:

0.0254

AC:

112

ESP6500EA

AF:

0.0921

AC:

792

ExAC

AF:

0.110

AC:

13327

Asia WGS

AF:

0.145

AC:

504

AN:

3478

EpiCase

AF:

0.0972

EpiControl

AF:

0.0939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.041

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

4.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.96

REVEL

Benign

0.085

Sift

Benign

0.077

Sift4G

Benign

0.15

Vest4

0.071

ClinPred

0.023

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.27

Mutation Taster

=96/4

polymorphism (auto)

(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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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