chr13-46651191-G-A

Position:

• chr13-46651191-G-A

Variant summary

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

The NM_001164211.2(LRCH1):​c.452+846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,032 control chromosomes in the GnomAD database, including 26,722 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 0.59 (26722 hom., cov: 32)
• Consequence: LRCH1 NM_001164211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRCH1	NM_001164211.2	c.452+846G>A		intron_variant		ENST00000389797.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRCH1	ENST00000389797.8	c.452+846G>A		intron_variant		1	NM_001164211.2
LRCH1	ENST00000311191.10	c.452+846G>A		intron_variant		1		P3
LRCH1	ENST00000389798.7	c.452+846G>A		intron_variant		1		A1
LRCH1	ENST00000443945.6	n.679+846G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90075 AN: 151912 Hom.: 26694 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.593 AC: 90145 AN: 152032 Hom.: 26722 Cov.: 32 AF XY: 0.597 AC XY: 44345 AN XY: 74332

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.594

Alfa AF: 0.575 Hom.: 10197

Bravo AF: 0.589

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.72

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: rs1773126; hg19: chr13-47225326;