rs2544165

Positions:

• chr7-134235691-G-A
• chr7-134235691-G-C

Variant summary

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

The NM_144648.3(LRGUK):​c.1984-11865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,942 control chromosomes in the GnomAD database, including 16,739 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 0.47 (16739 hom., cov: 32)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.1984-11865G>A		intron_variant		ENST00000285928.3	NP_653249.1
LRGUK	XM_024446659.2	c.1984-11865G>A		intron_variant			XP_024302427.1
LRGUK	XM_024446661.2	c.1984-11865G>A		intron_variant			XP_024302429.1
LRGUK	XM_047419890.1	c.1777-11865G>A		intron_variant			XP_047275846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.1984-11865G>A		intron_variant		1	NM_144648.3	ENSP00000285928.2

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70674 AN: 151824 Hom.: 16687 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.466 AC: 70783 AN: 151942 Hom.: 16739 Cov.: 32 AF XY: 0.466 AC XY: 34576 AN XY: 74264

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.453

Alfa AF: 0.464 Hom.: 22680

Bravo AF: 0.475

Asia WGS AF: 0.401 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.43

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: rs2544165; hg19: chr7-133920443;