NM_003667.4:c.1407-325G>A

Variant names:

• chr12-71579953-G-A
• rs73146224
• NM_003667.4:c.1407-325G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003667.4(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 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 0 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]

LOC124902963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.1407-325G>A		intron_variant	Intron 15 of 17	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.1407-325G>A		intron_variant	Intron 15 of 17	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.1335-325G>A		intron_variant	Intron 14 of 16	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.1191-325G>A		intron_variant	Intron 14 of 16	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.1788-325G>A		intron_variant	Intron 16 of 19	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

African (AFR) AF: 0.00403 AC: 167 AN: 41486

American (AMR) AF: 0.0112 AC: 172 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4816

European-Finnish (FIN) AF: 0.00312 AC: 33 AN: 10566

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1625 AN: 67986

Other (OTH) AF: 0.0123 AC: 26 AN: 2106

Alfa AF: 0.0201 Hom.: 54

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
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73146224; hg19: chr12-71973733;