12-71535142-C-T

Variant names:

• chr12-71535142-C-T
• rs142698551
• NM_003667.4:c.384C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_003667.4(LGR5):​c.384C>T​(p.His128His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,611,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: LGR5 NM_003667.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71
• Publications: 1 publications found

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]

LOC105369833 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 12-71535142-C-T is Benign according to our data. Variant chr12-71535142-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 740082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003667.4. 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
	LGR5	NM_003667.4	MANE Select	c.384C>T	p.His128His	synonymous	Exon 4 of 18	NP_003658.1	O75473-1
	LGR5	NM_001277226.2		c.384C>T	p.His128His	synonymous	Exon 4 of 17	NP_001264155.1	O75473-2
	LGR5	NM_001277227.2		c.384C>T	p.His128His	synonymous	Exon 4 of 17	NP_001264156.1	O75473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.384C>T	p.His128His	synonymous	Exon 4 of 18	ENSP00000266674.4	O75473-1
	LGR5	ENST00000540815.2	TSL:1	c.384C>T	p.His128His	synonymous	Exon 4 of 17	ENSP00000441035.2	O75473-2
	LGR5	ENST00000536515.5	TSL:1	c.384C>T	p.His128His	synonymous	Exon 4 of 17	ENSP00000443033.1	O75473-3

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 250880 AF XY: 0.000184

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.0000733 AC: 107 AN: 1459138 Hom.: 0 Cov.: 28 AF XY: 0.0000702 AC XY: 51 AN XY: 726122

African (AFR) AF: 0.00159 AC: 53 AN: 33426

American (AMR) AF: 0.000358 AC: 16 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26108

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39648

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110016

Other (OTH) AF: 0.000216 AC: 13 AN: 60306

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74448

African (AFR) AF: 0.00137 AC: 57 AN: 41558

American (AMR) AF: 0.000654 AC: 10 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.000733

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142698551; hg19: chr12-71928922;