Genetic Variant 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135217.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC23	NM_001135217.2	MANE Select	c.950T>A	p.Val317Glu	missense	Exon 7 of 8	NP_001128689.1	Q53EV4-1
LRRC23	NM_201650.3		c.950T>A	p.Val317Glu	missense	Exon 7 of 8	NP_964013.1	Q53EV4-1
LRRC23	NM_006992.4		c.759-970T>A		intron	N/A	NP_008923.1	Q53EV4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC23	ENST00000443597.7	TSL:1 MANE Select	c.950T>A	p.Val317Glu	missense	Exon 7 of 8	ENSP00000390932.2	Q53EV4-1
LRRC23	ENST00000007969.12	TSL:1	c.950T>A	p.Val317Glu	missense	Exon 7 of 8	ENSP00000007969.8	Q53EV4-1
LRRC23	ENST00000323702.9	TSL:1	c.759-970T>A		intron	N/A	ENSP00000317464.5	Q53EV4-2

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 v4.9

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

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.035

MetaRNN

Benign

0.000023

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.73

PhyloP100

4.7

PrimateAI

Benign

0.47

PROVEAN

Benign

2.9

REVEL

Benign

0.14

Sift

Benign

0.53

Sift4G

Benign

1.0

Polyphen

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over