1-202310191-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000367278.8(LGR6):​c.1407-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,613,508 control chromosomes in the GnomAD database, including 163 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 10 hom., cov: 32)
Exomes 𝑓: 0.013 ( 153 hom. )

Consequence

LGR6
ENST00000367278.8 splice_region, intron

Scores

2
Splicing: ADA: 0.0002987
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 1-202310191-C-G is Benign according to our data. Variant chr1-202310191-C-G is described in ClinVar as [Benign]. Clinvar id is 777562.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00972 (1480/152274) while in subpopulation NFE AF= 0.0166 (1129/68018). AF 95% confidence interval is 0.0158. There are 10 homozygotes in gnomad4. There are 648 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LGR6NM_001017403.2 linkuse as main transcriptc.1407-6C>G splice_region_variant, intron_variant ENST00000367278.8 NP_001017403.1 Q9HBX8-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LGR6ENST00000367278.8 linkuse as main transcriptc.1407-6C>G splice_region_variant, intron_variant 1 NM_001017403.2 ENSP00000356247.3 Q9HBX8-3
LGR6ENST00000255432.11 linkuse as main transcriptc.1251-6C>G splice_region_variant, intron_variant 1 ENSP00000255432.7 Q9HBX8-2
LGR6ENST00000439764.2 linkuse as main transcriptc.990-6C>G splice_region_variant, intron_variant 1 ENSP00000387869.2 Q9HBX8-1
LGR6ENST00000487787.5 linkuse as main transcriptn.*307-6C>G splice_region_variant, intron_variant 2 ENSP00000422143.1 D6R9F0

Frequencies

GnomAD3 genomes
AF:
0.00973
AC:
1481
AN:
152156
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00348
Gnomad AMI
AF:
0.0252
Gnomad AMR
AF:
0.00655
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00490
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0166
Gnomad OTH
AF:
0.00957
GnomAD3 exomes
AF:
0.00886
AC:
2219
AN:
250506
Hom.:
15
AF XY:
0.00890
AC XY:
1204
AN XY:
135302
show subpopulations
Gnomad AFR exome
AF:
0.00345
Gnomad AMR exome
AF:
0.00328
Gnomad ASJ exome
AF:
0.000899
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00340
Gnomad FIN exome
AF:
0.00735
Gnomad NFE exome
AF:
0.0153
Gnomad OTH exome
AF:
0.00851
GnomAD4 exome
AF:
0.0134
AC:
19520
AN:
1461234
Hom.:
153
Cov.:
31
AF XY:
0.0130
AC XY:
9475
AN XY:
726870
show subpopulations
Gnomad4 AFR exome
AF:
0.00314
Gnomad4 AMR exome
AF:
0.00385
Gnomad4 ASJ exome
AF:
0.000997
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00325
Gnomad4 FIN exome
AF:
0.00807
Gnomad4 NFE exome
AF:
0.0160
Gnomad4 OTH exome
AF:
0.0110
GnomAD4 genome
AF:
0.00972
AC:
1480
AN:
152274
Hom.:
10
Cov.:
32
AF XY:
0.00870
AC XY:
648
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00347
Gnomad4 AMR
AF:
0.00654
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00490
Gnomad4 NFE
AF:
0.0166
Gnomad4 OTH
AF:
0.00947
Alfa
AF:
0.0102
Hom.:
4
Bravo
AF:
0.00926
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0142
EpiControl
AF:
0.0154

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.14
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00030
dbscSNV1_RF
Benign
0.012
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146771876; hg19: chr1-202279319; API