chr12-71579953-G-A

Position:

• chr12-71579953-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000266674.10(LGR5):​c.1407-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,094 control chromosomes in the GnomAD database, including 24 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 0.014 (24 hom., cov: 32)
• Consequence: LGR5 ENST00000266674.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614

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]

LOC124902963 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2185/152094) while in subpopulation NFE AF= 0.0239 (1625/67986). AF 95% confidence interval is 0.0229. There are 24 homozygotes in gnomad4. There are 1002 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR5	NM_003667.4	c.1407-325G>A		intron_variant		ENST00000266674.10	NP_003658.1
LOC124902963	XR_007063365.1	n.125+1139C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.1407-325G>A		intron_variant		1	NM_003667.4	ENSP00000266674	P1
LGR5	ENST00000536515.5	c.1191-325G>A		intron_variant		1		ENSP00000443033
LGR5	ENST00000540815.2	c.1335-325G>A		intron_variant		1		ENSP00000441035
LGR5	ENST00000550851.5	n.1788-325G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2186 AN: 151976 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00404

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0144 AC: 2185 AN: 152094 Hom.: 24 Cov.: 32 AF XY: 0.0135 AC XY: 1002 AN XY: 74342

Gnomad4 AFR AF: 0.00403

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.00312

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00256 Hom.: 0

Bravo AF: 0.0139

Asia WGS AF: 0.0110 AC: 39 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs73146224; hg19: chr12-71973733;