1-202297508-A-C

Variant names:

• chr1-202297508-A-C
• rs1667247829
• NM_001017403.2:c.717A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001017403.2(LGR6):​c.717A>C​(p.Leu239Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,460,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L239L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: LGR6 NM_001017403.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001905
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.466 with no splicing effect.

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.717A>C	p.Leu239Leu	splice_region synonymous	Exon 7 of 18	NP_001017403.1	Q9HBX8-3
	LGR6	NM_021636.3		c.561A>C	p.Leu187Leu	splice_region synonymous	Exon 7 of 18	NP_067649.2	Q9HBX8-2
	LGR6	NM_001017404.2		c.300A>C	p.Leu100Leu	splice_region synonymous	Exon 5 of 16	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.717A>C	p.Leu239Leu	splice_region synonymous	Exon 7 of 18	ENSP00000356247.3	Q9HBX8-3
	LGR6	ENST00000255432.11	TSL:1	c.561A>C	p.Leu187Leu	splice_region synonymous	Exon 7 of 18	ENSP00000255432.7	Q9HBX8-2
	LGR6	ENST00000439764.2	TSL:1	c.300A>C	p.Leu100Leu	splice_region synonymous	Exon 5 of 16	ENSP00000387869.2	Q9HBX8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1460996 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726806

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111566

Other (OTH) AF: 0.0000166 AC: 1 AN: 60352

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.8
DANN	Benign	0.63
PhyloP100		0.47
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.036
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: rs1667247829; hg19: chr1-202266636;