rs6678914

Positions:

• chr1-202218048-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017403.2(LGR6):​c.213-7375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,974 control chromosomes in the GnomAD database, including 10,531 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 0.37 (10531 hom., cov: 32)
• Consequence: LGR6 NM_001017403.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR6	NM_001017403.2	c.213-7375G>A		intron_variant		ENST00000367278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGR6	ENST00000367278.8	c.213-7375G>A		intron_variant		1	NM_001017403.2	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56057 AN: 151856 Hom.: 10523 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.369 AC: 56105 AN: 151974 Hom.: 10531 Cov.: 32 AF XY: 0.366 AC XY: 27155 AN XY: 74274

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.372

Alfa AF: 0.394 Hom.: 8016

Bravo AF: 0.356

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs6678914; hg19: chr1-202187176;