chr1-202218048-G-A

Variant names:

• chr1-202218048-G-A
• rs6678914
• NM_001017403.2:c.213-7375G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 69 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	NM_001017403.2	MANE Select	c.213-7375G>A		intron	N/A	NP_001017403.1
	LGR6	NM_021636.3		c.57-7375G>A		intron	N/A	NP_067649.2
	LGR6	NM_001017404.2		c.83+3811G>A		intron	N/A	NP_001017404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR6	ENST00000367278.8	TSL:1 MANE Select	c.213-7375G>A		intron	N/A	ENSP00000356247.3
	LGR6	ENST00000255432.11	TSL:1	c.57-7375G>A		intron	N/A	ENSP00000255432.7
	LGR6	ENST00000439764.2	TSL:1	c.83+3811G>A		intron	N/A	ENSP00000387869.2

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

African (AFR) AF: 0.328 AC: 13570 AN: 41406

American (AMR) AF: 0.311 AC: 4755 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5180

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4814

European-Finnish (FIN) AF: 0.464 AC: 4895 AN: 10552

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27722 AN: 67956

Other (OTH) AF: 0.372 AC: 786 AN: 2112

Alfa AF: 0.389 Hom.: 28130

Bravo AF: 0.356

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs6678914; hg19: chr1-202187176;