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GeneBe

12-71578813-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003667.4(LGR5):c.1290G>T(p.Ser430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,607,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 1 hom. )

Consequence

LGR5
NM_003667.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.974
Variant links:
Genes affected
LGR5 (HGNC:4504): (leucine rich repeat containing G protein-coupled receptor 5) The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-71578813-G-T is Benign according to our data. Variant chr12-71578813-G-T is described in ClinVar as [Benign]. Clinvar id is 779529.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.974 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00455 (693/152202) while in subpopulation AFR AF= 0.0161 (667/41532). AF 95% confidence interval is 0.0151. There are 6 homozygotes in gnomad4. There are 324 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGR5NM_003667.4 linkuse as main transcriptc.1290G>T p.Ser430= synonymous_variant 15/18 ENST00000266674.10
LOC124902963XR_007063365.1 linkuse as main transcriptn.126-1782C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGR5ENST00000266674.10 linkuse as main transcriptc.1290G>T p.Ser430= synonymous_variant 15/181 NM_003667.4 P1O75473-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00453
AC:
689
AN:
152084
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0160
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000983
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00110
AC:
272
AN:
246920
Hom.:
1
AF XY:
0.000764
AC XY:
102
AN XY:
133438
show subpopulations
Gnomad AFR exome
AF:
0.0157
Gnomad AMR exome
AF:
0.000483
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000501
GnomAD4 exome
AF:
0.000447
AC:
651
AN:
1454952
Hom.:
1
Cov.:
30
AF XY:
0.000384
AC XY:
278
AN XY:
723586
show subpopulations
Gnomad4 AFR exome
AF:
0.0168
Gnomad4 AMR exome
AF:
0.000525
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.000832
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00455
AC:
693
AN:
152202
Hom.:
6
Cov.:
32
AF XY:
0.00435
AC XY:
324
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0161
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00148
Hom.:
2
Bravo
AF:
0.00506
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

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 testingInvitaeJun 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
0.46
Dann
Benign
0.78

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

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

Other links and lift over

dbSNP: rs80013431; hg19: chr12-71972593; API