1-202194068-C-G

Variant names:

• chr1-202194068-C-G
• rs1437113234
• NM_001017403.2:c.79C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017403.2(LGR6):​c.79C>G​(p.Gln27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q27K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGR6 NM_001017403.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 3 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]

ENSG00000295211 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0728333).

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.79C>G	p.Gln27Glu	missense	Exon 1 of 18	NP_001017403.1	Q9HBX8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	ENST00000367278.8	TSL:1 MANE Select	c.79C>G	p.Gln27Glu	missense	Exon 1 of 18	ENSP00000356247.3	Q9HBX8-3
	LGR6	ENST00000904634.1		c.79C>G	p.Gln27Glu	missense	Exon 1 of 19	ENSP00000574693.1
	LGR6	ENST00000904651.1		c.79C>G	p.Gln27Glu	missense	Exon 1 of 19	ENSP00000574710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 75274 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1291622 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 636894

African (AFR) AF: 0.00 AC: 0 AN: 26540

American (AMR) AF: 0.00 AC: 0 AN: 21370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21228

East Asian (EAS) AF: 0.00 AC: 0 AN: 29296

South Asian (SAS) AF: 0.00 AC: 0 AN: 66274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1036846

Other (OTH) AF: 0.00 AC: 0 AN: 53270

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.74
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.093
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.25		Gain of relative solvent accessibility (P = 0.09)
MVP		0.63
MPC		0.28
ClinPred		0.041	T
GERP RS		1.5
PromoterAI		0.045	Neutral
Varity_R		0.095
gMVP		0.19
Mutation Taster		=96/4	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: rs1437113234; hg19: chr1-202163196;