13-46671856-T-C

Variant names:

• chr13-46671856-T-C
• rs9645940
• NM_001164211.2:c.579+2700T>C

Variant summary

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

The NM_001164211.2(LRCH1):​c.579+2700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,190 control chromosomes in the GnomAD database, including 1,247 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 0.12 (1247 hom., cov: 32)
• Consequence: LRCH1 NM_001164211.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRCH1	NM_001164211.2	c.579+2700T>C		intron_variant	Intron 3 of 19	ENST00000389797.8	NP_001157683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRCH1	ENST00000389797.8	c.579+2700T>C		intron_variant	Intron 3 of 19	1	NM_001164211.2	ENSP00000374447.3
LRCH1	ENST00000389798.7	c.579+2700T>C		intron_variant	Intron 3 of 18	1		ENSP00000374448.3
LRCH1	ENST00000311191.10	c.579+2700T>C		intron_variant	Intron 3 of 18	1		ENSP00000308493.5
LRCH1	ENST00000443945.6	n.806+2700T>C		intron_variant	Intron 3 of 12	1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18598 AN: 152072 Hom.: 1244 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.122 AC: 18628 AN: 152190 Hom.: 1247 Cov.: 32 AF XY: 0.122 AC XY: 9098 AN XY: 74430

African (AFR) AF: 0.158 AC: 6570 AN: 41506

American (AMR) AF: 0.133 AC: 2036 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1192 AN: 5180

South Asian (SAS) AF: 0.138 AC: 666 AN: 4822

European-Finnish (FIN) AF: 0.0393 AC: 417 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6909 AN: 67992

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.113 Hom.: 1308

Bravo AF: 0.134

Asia WGS AF: 0.182 AC: 634 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	1.8
DANN	Benign	0.50
PhyloP100		-0.22
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: rs9645940; hg19: chr13-47245991;