Variant 13-46685996-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001164211.2(LRCH1):c.777A>G(p.Gln259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,610,136 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 180 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 152 hom. )

Consequence

LRCH1
NM_001164211.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

LRCH1 (HGNC:20309): (leucine rich repeats and calponin homology domain containing 1) This gene encodes a protein with a leucine-rich repeat and a calponin homology domain. Polymorphism in this gene may be associated with susceptibililty to knee osteoarthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2010]

LRCH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 13-46685996-A-G is Benign according to our data. Variant chr13-46685996-A-G is described in ClinVar as [Benign]. Clinvar id is 782306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.894 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH1	NM_001164211.2 linkuse as main transcript	c.777A>G	p.Gln259=	synonymous_variant	5/20	ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8 linkuse as main transcript	c.777A>G	p.Gln259=	synonymous_variant	5/20	1	NM_001164211.2	ENSP00000374447		Q9Y2L9-3

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3912

AN:

152132

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00930

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00640

AC:

1583

AN:

247336

Hom.:

AF XY:

0.00481

AC XY:

643

AN XY:

133690

show subpopulations

Gnomad AFR exome

AF:

0.0870

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.000441

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.00350

GnomAD4 exome

AF:

0.00259

AC:

3770

AN:

1457886

Hom.:

152

Cov.:

AF XY:

0.00230

AC XY:

1665

AN XY:

725050

show subpopulations

Gnomad4 AFR exome

AF:

0.0887

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00283

Gnomad4 EAS exome

AF:

0.00179

Gnomad4 SAS exome

AF:

0.000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000945

Gnomad4 OTH exome

AF:

0.00607

GnomAD4 genome

AF:

0.0257

AC:

3918

AN:

152250

Hom.:

180

Cov.:

AF XY:

0.0250

AC XY:

1863

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.00683

Hom.:

Bravo

AF:

0.0286

EpiCase

AF:

0.000110

EpiControl

AF:

0.000597

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.8

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over