rs17761994

Variant names:

• chr7-134158789-A-G
• rs17761994
• NM_144648.3:c.795+630A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.795+630A>G		intron_variant	Intron 6 of 19	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.795+630A>G		intron_variant	Intron 6 of 19	1	NM_144648.3	ENSP00000285928.2
LRGUK	ENST00000695542.2	c.795+630A>G		intron_variant	Intron 6 of 15			ENSP00000511999.1
LRGUK	ENST00000645682.1	c.795+630A>G		intron_variant	Intron 6 of 15			ENSP00000495637.1

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

African (AFR) AF: 0.0108 AC: 450 AN: 41568

American (AMR) AF: 0.0420 AC: 643 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4818

European-Finnish (FIN) AF: 0.0627 AC: 665 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4501 AN: 67990

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0519 Hom.: 170

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17761994; hg19: chr7-133843542;