13-46593768-A-G

Variant names:

• chr13-46593768-A-G
• rs912428
• NM_001164211.2:c.307+40065A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164211.2(LRCH1):​c.307+40065A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,116 control chromosomes in the GnomAD database, including 54,205 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 0.84 (54205 hom., cov: 30)
• Consequence: LRCH1 NM_001164211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRCH1	NM_001164211.2	c.307+40065A>G		intron_variant	Intron 1 of 19	ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8	c.307+40065A>G		intron_variant	Intron 1 of 19	1	NM_001164211.2	ENSP00000374447.3
LRCH1	ENST00000389798.7	c.307+40065A>G		intron_variant	Intron 1 of 18	1		ENSP00000374448.3
LRCH1	ENST00000311191.10	c.307+40065A>G		intron_variant	Intron 1 of 18	1		ENSP00000308493.5
LRCH1	ENST00000443945.6	n.534+40065A>G		intron_variant	Intron 1 of 12	1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128142 AN: 151998 Hom.: 54181 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.843 AC: 128218 AN: 152116 Hom.: 54205 Cov.: 30 AF XY: 0.842 AC XY: 62641 AN XY: 74356

African (AFR) AF: 0.876 AC: 36349 AN: 41500

American (AMR) AF: 0.898 AC: 13726 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3157 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4722 AN: 5168

South Asian (SAS) AF: 0.834 AC: 4015 AN: 4814

European-Finnish (FIN) AF: 0.783 AC: 8276 AN: 10566

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55205 AN: 67986

Other (OTH) AF: 0.850 AC: 1795 AN: 2112

Alfa AF: 0.826 Hom.: 18628

Bravo AF: 0.853

Asia WGS AF: 0.825 AC: 2869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.018
DANN	Benign	0.41
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs912428; hg19: chr13-47167903;