13-46712803-C-G

Position:

• chr13-46712803-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164211.2(LRCH1):​c.1654+206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 152,122 control chromosomes in the GnomAD database, including 34,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34878 hom., cov: 33)
• Consequence: LRCH1 NM_001164211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRCH1	NM_001164211.2	c.1654+206C>G		intron_variant		ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8	c.1654+206C>G		intron_variant		1	NM_001164211.2	ENSP00000374447.3
LRCH1	ENST00000389798.7	c.1654+206C>G		intron_variant		1		ENSP00000374448.3
LRCH1	ENST00000311191.10	c.1654+206C>G		intron_variant		1		ENSP00000308493.5

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102600 AN: 152004 Hom.: 34855 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.675

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.675 AC: 102678 AN: 152122 Hom.: 34878 Cov.: 33 AF XY: 0.679 AC XY: 50521 AN XY: 74356

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.672

Alfa AF: 0.649 Hom.: 3787

Bravo AF: 0.677

Asia WGS AF: 0.679 AC: 2362 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs2762130; hg19: chr13-47286938;