rs12670589

Variant names:

• chr7-134160344-C-G
• rs12670589
• NM_144648.3:c.795+2185C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144648.3(LRGUK):​c.795+2185C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,010 control chromosomes in the GnomAD database, including 4,488 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 0.22 (4488 hom., cov: 33)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 2 publications found

Genes affected

LRGUK (HGNC:21964): (leucine rich repeats and guanylate kinase domain containing) Predicted to enable guanylate kinase activity. Predicted to be involved in axoneme assembly and spermatogenesis. Predicted to be located in acrosomal vesicle and manchette. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.795+2185C>G		intron_variant	Intron 6 of 19	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.795+2185C>G		intron_variant	Intron 6 of 19	1	NM_144648.3	ENSP00000285928.2
LRGUK	ENST00000695542.2	c.795+2185C>G		intron_variant	Intron 6 of 15			ENSP00000511999.1
LRGUK	ENST00000645682.1	c.795+2185C>G		intron_variant	Intron 6 of 15			ENSP00000495637.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32917 AN: 151894 Hom.: 4489 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.217 AC: 32913 AN: 152010 Hom.: 4488 Cov.: 33 AF XY: 0.216 AC XY: 16051 AN XY: 74276

African (AFR) AF: 0.0617 AC: 2561 AN: 41494

American (AMR) AF: 0.223 AC: 3405 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3470

East Asian (EAS) AF: 0.190 AC: 982 AN: 5168

South Asian (SAS) AF: 0.357 AC: 1724 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2205 AN: 10518

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20248 AN: 67938

Other (OTH) AF: 0.226 AC: 477 AN: 2114

Alfa AF: 0.239 Hom.: 551

Bravo AF: 0.207

Asia WGS AF: 0.232 AC: 808 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.64
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs12670589; hg19: chr7-133845097;