rs389277

Variant names:

• chr7-134233586-T-C
• rs389277
• NM_144648.3:c.1983+11668T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144648.3(LRGUK):​c.1983+11668T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,312 control chromosomes in the GnomAD database, including 455 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 0.052 (455 hom., cov: 32)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 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 (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.1983+11668T>C		intron_variant	Intron 16 of 19	ENST00000285928.3	NP_653249.1
LRGUK	XM_024446659.2	c.1983+11668T>C		intron_variant	Intron 16 of 19		XP_024302427.1
LRGUK	XM_024446661.2	c.1983+11668T>C		intron_variant	Intron 16 of 19		XP_024302429.1
LRGUK	XM_047419890.1	c.1776+11668T>C		intron_variant	Intron 14 of 17		XP_047275846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.1983+11668T>C		intron_variant	Intron 16 of 19	1	NM_144648.3	ENSP00000285928.2

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7874 AN: 152194 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00564

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0519 AC: 7903 AN: 152312 Hom.: 455 Cov.: 32 AF XY: 0.0517 AC XY: 3853 AN XY: 74488

African (AFR) AF: 0.130 AC: 5383 AN: 41556

American (AMR) AF: 0.0465 AC: 711 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5182

South Asian (SAS) AF: 0.0613 AC: 296 AN: 4828

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00564 AC: 384 AN: 68026

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0356 Hom.: 36

Bravo AF: 0.0593

Asia WGS AF: 0.0970 AC: 336 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	3.1
DANN	Benign	0.50
PhyloP100		0.049
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: rs389277; hg19: chr7-133918338;