NM_001164211.2:c.452+846G>A

Variant names:

• chr13-46651191-G-A
• rs1773126
• NM_001164211.2:c.452+846G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164211.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH1	NM_001164211.2	MANE Select	c.452+846G>A		intron	N/A	NP_001157683.2
	LRCH1	NM_015116.3		c.452+846G>A		intron	N/A	NP_055931.2
	LRCH1	NM_001164213.2		c.452+846G>A		intron	N/A	NP_001157685.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH1	ENST00000389797.8	TSL:1 MANE Select	c.452+846G>A		intron	N/A	ENSP00000374447.3
	LRCH1	ENST00000389798.7	TSL:1	c.452+846G>A		intron	N/A	ENSP00000374448.3
	LRCH1	ENST00000311191.10	TSL:1	c.452+846G>A		intron	N/A	ENSP00000308493.5

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

African (AFR) AF: 0.561 AC: 23247 AN: 41428

American (AMR) AF: 0.646 AC: 9872 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2087 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3314 AN: 5180

South Asian (SAS) AF: 0.676 AC: 3262 AN: 4824

European-Finnish (FIN) AF: 0.647 AC: 6837 AN: 10566

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39620 AN: 67980

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.575 Hom.: 11457

Bravo AF: 0.589

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.72
PhyloP100		-1.5
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: rs1773126; hg19: chr13-47225326;