rs17761994

Positions:

• chr7-134158789-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.795+630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 152,252 control chromosomes in the GnomAD database, including 217 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 0.044 (217 hom., cov: 33)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRGUK	NM_144648.3	c.795+630A>G		intron_variant		ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRGUK	ENST00000285928.3	c.795+630A>G		intron_variant		1	NM_144648.3	P2
LRGUK	ENST00000645682.1	c.795+630A>G		intron_variant				A2
LRGUK	ENST00000695542.2	c.795+630A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6700 AN: 152134 Hom.: 217 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0440 AC: 6699 AN: 152252 Hom.: 217 Cov.: 33 AF XY: 0.0426 AC XY: 3175 AN XY: 74444

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0627

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0575 Hom.: 150

Bravo AF: 0.0413

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.079
DANN	Benign	0.56

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: rs17761994; hg19: chr7-133843542;