rs17167492

Positions:

• chr7-134143268-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144648.3(LRGUK):​c.588+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 706,352 control chromosomes in the GnomAD database, including 7,038 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 0.12 (1423 hom., cov: 33)
  • Exomes 𝑓: 0.13 (5615 hom.)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRGUK	NM_144648.3	c.588+106G>A		intron_variant		ENST00000285928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRGUK	ENST00000285928.3	c.588+106G>A		intron_variant		1	NM_144648.3	P2
LRGUK	ENST00000645682.1	c.588+106G>A		intron_variant				A2
LRGUK	ENST00000695542.2	c.588+106G>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18476 AN: 152030 Hom.: 1420 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.126 AC: 69654 AN: 554204 Hom.: 5615 AF XY: 0.127 AC XY: 38028 AN XY: 300108

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0684

Gnomad4 NFE exome AF: 0.0954

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.122 AC: 18502 AN: 152148 Hom.: 1423 Cov.: 33 AF XY: 0.123 AC XY: 9121 AN XY: 74382

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0598

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.137

Alfa AF: 0.110 Hom.: 147

Bravo AF: 0.132

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.55

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: rs17167492; hg19: chr7-133828021;