rs13246630

Variant names:

• chr7-134136866-A-G
• rs13246630
• NM_144648.3:c.298-157A>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.298-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,200 control chromosomes in the GnomAD database, including 29,596 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 0.62 (29596 hom., cov: 34)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.298-157A>G		intron_variant	Intron 1 of 19	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.298-157A>G		intron_variant	Intron 1 of 19	1	NM_144648.3	ENSP00000285928.2
LRGUK	ENST00000695542.2	c.298-157A>G		intron_variant	Intron 1 of 15			ENSP00000511999.1
LRGUK	ENST00000645682.1	c.298-157A>G		intron_variant	Intron 1 of 15			ENSP00000495637.1
LRGUK	ENST00000473068.1	n.308-157A>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94285 AN: 152082 Hom.: 29572 Cov.: 34

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.620 AC: 94353 AN: 152200 Hom.: 29596 Cov.: 34 AF XY: 0.621 AC XY: 46220 AN XY: 74402

African (AFR) AF: 0.676 AC: 28088 AN: 41520

American (AMR) AF: 0.600 AC: 9170 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3472

East Asian (EAS) AF: 0.483 AC: 2503 AN: 5182

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4820

European-Finnish (FIN) AF: 0.721 AC: 7643 AN: 10606

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40721 AN: 67986

Other (OTH) AF: 0.607 AC: 1283 AN: 2114

Alfa AF: 0.601 Hom.: 86800

Bravo AF: 0.615

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.76
PhyloP100		-1.1
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: rs13246630; hg19: chr7-133821619;