chr12-71556676-C-T

Variant names:

• chr12-71556676-C-T
• rs140637499
• NM_003667.4:c.702C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_003667.4(LGR5):​c.702C>T​(p.His234His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,610,018 control chromosomes in the GnomAD database, including 6 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 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: LGR5 NM_003667.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.702C>T	p.His234His	synonymous_variant	Exon 6 of 18	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.702C>T	p.His234His	synonymous_variant	Exon 6 of 18	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.702C>T	p.His234His	synonymous_variant	Exon 6 of 17	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.486C>T	p.His162His	synonymous_variant	Exon 5 of 17	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.799C>T		non_coding_transcript_exon_variant	Exon 6 of 20	2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00116 AC: 291 AN: 251296 Hom.: 1 AF XY: 0.00118 AC XY: 160 AN XY: 135812

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00151 AC: 2194 AN: 1457690 Hom.: 6 Cov.: 28 AF XY: 0.00147 AC XY: 1066 AN XY: 725512

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00184

Gnomad4 OTH exome AF: 0.000780

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74494

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00119

EpiCase AF: 0.00169

EpiControl AF: 0.00225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.2
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs140637499; hg19: chr12-71950456;