dbSNP rs145823585: LRRC10:p.Leu120Leu (chr12-69610479-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_201550.4(LRRC10):c.360C>T(p.Leu120Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00969 in 1,614,188 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 95 hom. )

Consequence

LRRC10
NM_201550.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0310

Publications

2 publications found

Variant links:

Genes affected

LRRC10 (HGNC:20264): (leucine rich repeat containing 10) Predicted to enable actin binding activity. Predicted to be involved in cardiac muscle cell development. Predicted to be located in myofibril. Predicted to be active in cytoskeleton and sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

LRRC10 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

LRRC10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-69610479-G-A is Benign according to our data. Variant chr12-69610479-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.031 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC10	NM_201550.4 link	c.360C>T	p.Leu120Leu	synonymous_variant	Exon 1 of 1	ENST00000361484.5	NP_963844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC10	ENST00000361484.5 link	c.360C>T	p.Leu120Leu	synonymous_variant	Exon 1 of 1	6	NM_201550.4	ENSP00000355166.3

Frequencies

GnomAD3 genomes

AF:

0.00780

AC:

1188

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00770

AC:

1935

AN:

251196

AF XY:

0.00793

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.00882

GnomAD4 exome

AF:

0.00989

AC:

14459

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

7030

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

33480

American (AMR)

AF:

0.00391

AC:

175

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000842

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00285

AC:

246

AN:

86258

European-Finnish (FIN)

AF:

0.0183

AC:

976

AN:

53380

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0112

AC:

12459

AN:

1112010

Other (OTH)

AF:

0.00810

AC:

489

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

998

1996

2994

3992

4990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00780

AC:

1188

AN:

152336

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

583

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41590

American (AMR)

AF:

0.00588

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0165

AC:

175

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0118

AC:

802

AN:

68030

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00873

Hom.:

Bravo

AF:

0.00649

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 21, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dilated Cardiomyopathy, Dominant

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.7

(source)

DANN

Benign

0.72

PhyloP100

0.031

PromoterAI

0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over