1-202276370-C-T

Variant names:

• chr1-202276370-C-T
• rs148637417
• NM_001017403.2:c.493C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3 BP4

The NM_001017403.2(LGR6):​c.493C>T​(p.Arg165Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R165H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: LGR6 NM_001017403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 5 publications found

Genes affected

LGR6 (HGNC:19719): (leucine rich repeat containing G protein-coupled receptor 6) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, PROVEAN [when max_spliceai, MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.2695044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	NM_001017403.2	MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 5 of 18	NP_001017403.1	Q9HBX8-3
	LGR6	NM_021636.3		c.337C>T	p.Arg113Cys	missense	Exon 5 of 18	NP_067649.2	Q9HBX8-2
	LGR6	NM_001017404.2		c.300-21138C>T		intron	N/A	NP_001017404.1	Q9HBX8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	ENST00000367278.8	TSL:1 MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 5 of 18	ENSP00000356247.3	Q9HBX8-3
	LGR6	ENST00000255432.11	TSL:1	c.337C>T	p.Arg113Cys	missense	Exon 5 of 18	ENSP00000255432.7	Q9HBX8-2
	LGR6	ENST00000439764.2	TSL:1	c.300-21138C>T		intron	N/A	ENSP00000387869.2	Q9HBX8-1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000131 AC: 33 AN: 251258 AF XY: 0.000125

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000958 AC: 140 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.0000990 AC XY: 72 AN XY: 727232

African (AFR) AF: 0.00176 AC: 59 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111998

Other (OTH) AF: 0.000149 AC: 9 AN: 60396

GnomAD4 genome AF: 0.000492 AC: 75 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74492

African (AFR) AF: 0.00171 AC: 71 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000231 Hom.: 0

Bravo AF: 0.000427

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.063	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.89
MVP		0.93
MPC		1.1
ClinPred		0.33	T
GERP RS		5.1
Varity_R		0.83
gMVP		0.61
Mutation Taster		=63/37	polymorphism

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: rs148637417; hg19: chr1-202245498; COSMIC: COSV99707527;