rs511411

Positions:

• chr7-134145136-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+1974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,136 control chromosomes in the GnomAD database, including 4,933 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 0.23 (4933 hom., cov: 32)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.588+1974G>A		intron_variant		ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.588+1974G>A		intron_variant		1	NM_144648.3	ENSP00000285928	P2
LRGUK	ENST00000645682.1	c.588+1974G>A		intron_variant				ENSP00000495637	A2
LRGUK	ENST00000695542.2	c.588+1974G>A		intron_variant				ENSP00000511999	A2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34388 AN: 152018 Hom.: 4935 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.226 AC: 34383 AN: 152136 Hom.: 4933 Cov.: 32 AF XY: 0.224 AC XY: 16691 AN XY: 74370

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.234

Alfa AF: 0.302 Hom.: 14790

Bravo AF: 0.216

Asia WGS AF: 0.227 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.42

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: rs511411; hg19: chr7-133829889;