dbSNP rs1057077: LRRC23:p.Val317Glu (chr12-6912921-T-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_001135217.2(LRRC23):c.950T>A(p.Val317Glu) variant causes a missense change. The variant allele was found at a frequency of 0.298 in 1,613,650 control chromosomes in the GnomAD database, including 77,324 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.

Frequency

Genomes: 𝑓 0.38 ( 12452 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64872 hom. )

Consequence

LRRC23
NM_001135217.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.70

Publications

40 publications found

Variant links:

Genes affected

LRRC23 (HGNC:19138): (leucine rich repeat containing 23) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC23 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=2.2957329E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC23	NM_001135217.2 link	c.950T>A	p.Val317Glu	missense_variant	Exon 7 of 8	ENST00000443597.7	NP_001128689.1	Q53EV4-1A8K8K2
LRRC23	NM_201650.3 link	c.950T>A	p.Val317Glu	missense_variant	Exon 7 of 8		NP_964013.1	Q53EV4-1A8K8K2
LRRC23	NM_006992.4 link	c.759-970T>A		intron_variant	Intron 6 of 6		NP_008923.1	Q53EV4-2A8K8K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC23	ENST00000443597.7 link	c.950T>A	p.Val317Glu	missense_variant	Exon 7 of 8	1	NM_001135217.2	ENSP00000390932.2		Q53EV4-1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56942

AN:

151692

Hom.:

12430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.297

AC:

74574

AN:

251474

AF XY:

0.297

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.285

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.290

AC:

424413

AN:

1461840

Hom.:

64872

Cov.:

AF XY:

0.292

AC XY:

212169

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.644

AC:

21560

AN:

33480

American (AMR)

AF:

0.230

AC:

10289

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

7288

AN:

26134

East Asian (EAS)

AF:

0.272

AC:

10804

AN:

39700

South Asian (SAS)

AF:

0.334

AC:

28784

AN:

86256

European-Finnish (FIN)

AF:

0.235

AC:

12563

AN:

53418

Middle Eastern (MID)

AF:

0.405

AC:

2336

AN:

5768

European-Non Finnish (NFE)

AF:

0.281

AC:

311943

AN:

1111968

Other (OTH)

AF:

0.312

AC:

18846

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19266

38531

57797

77062

96328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10470

20940

31410

41880

52350

<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:

0.376

AC:

57011

AN:

151810

Hom.:

12452

Cov.:

AF XY:

0.370

AC XY:

27483

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.625

AC:

25835

AN:

41356

American (AMR)

AF:

0.301

AC:

4586

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

945

AN:

3472

East Asian (EAS)

AF:

0.252

AC:

1299

AN:

5158

South Asian (SAS)

AF:

0.325

AC:

1560

AN:

4804

European-Finnish (FIN)

AF:

0.230

AC:

2423

AN:

10556

Middle Eastern (MID)

AF:

0.421

AC:

123

AN:

292

European-Non Finnish (NFE)

AF:

0.282

AC:

19144

AN:

67930

Other (OTH)

AF:

0.381

AC:

802

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1688

3376

5064

6752

8440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.309

Hom.:

2624

Bravo

AF:

0.387

TwinsUK

AF:

0.264

AC:

979

ALSPAC

AF:

0.265

AC:

1022

ESP6500AA

AF:

0.617

AC:

2718

ESP6500EA

AF:

0.280

AC:

2410

ExAC

AF:

0.304

AC:

36970

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

EpiCase

AF:

0.293

EpiControl

AF:

0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.035

.;T

MetaRNN

Benign

0.000023

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.73

N;N

PhyloP100

4.7

PrimateAI

Benign

0.47

PROVEAN

Benign

2.9

N;N

REVEL

Benign

0.14

Sift

Benign

0.53

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.048

MPC

0.23

ClinPred

0.0041

GERP RS

5.3

Varity_R

0.11

gMVP

0.14

Mutation Taster

=91/9

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