1-202297508-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001017403.2(LGR6):​c.717A>T​(p.Leu239Leu) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LGR6 NM_001017403.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0003506
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 1-202297508-A-T is Benign according to our data. Variant chr1-202297508-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3118593.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.4
DANN	Benign	0.64
PhyloP100		0.47
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
dbscSNV1_RF	Benign	0.014
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;