rs511411

Variant names:

• chr7-134145136-G-A
• rs511411
• NM_144648.3:c.588+1974G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144648.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRGUK	NM_144648.3	MANE Select	c.588+1974G>A		intron	N/A	NP_653249.1	Q96M69
	LRGUK	NM_001365700.3		c.588+1974G>A		intron	N/A	NP_001352629.1	A0A8Q3SI13
	LRGUK	NM_001365701.3		c.588+1974G>A		intron	N/A	NP_001352630.1	A0A2R8YEJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRGUK	ENST00000285928.3	TSL:1 MANE Select	c.588+1974G>A		intron	N/A	ENSP00000285928.2	Q96M69
	LRGUK	ENST00000695542.2		c.588+1974G>A		intron	N/A	ENSP00000511999.1	A0A8Q3SI13
	LRGUK	ENST00000645682.1		c.588+1974G>A		intron	N/A	ENSP00000495637.1	A0A2R8YEJ5

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

African (AFR) AF: 0.0620 AC: 2573 AN: 41518

American (AMR) AF: 0.230 AC: 3511 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3470

East Asian (EAS) AF: 0.191 AC: 987 AN: 5178

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4818

European-Finnish (FIN) AF: 0.220 AC: 2328 AN: 10584

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21351 AN: 67970

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.284 Hom.: 22349

Bravo AF: 0.216

Asia WGS AF: 0.227 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.42
PhyloP100		0.31
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: rs511411; hg19: chr7-133829889;