rs13246630

chr7-134136866-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LRGUK	NM_144648.3	c.298-157A>G		intron_variant		ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRGUK	ENST00000285928.3	c.298-157A>G		intron_variant		1	NM_144648.3	P2
LRGUK	ENST00000645682.1	c.298-157A>G		intron_variant				A2
LRGUK	ENST00000695542.2	c.298-157A>G		intron_variant				A2
LRGUK	ENST00000473068.1	n.308-157A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.607

Alfa AF: 0.594 Hom.: 53732

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

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: rs13246630; hg19: chr7-133821619;