chr7-134167429-C-G

Variant names:

• chr7-134167429-C-G
• rs892984
• NM_144648.3:c.939+3889C>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.939+3889C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,230 control chromosomes in the GnomAD database, including 1,679 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 0.13 (1679 hom., cov: 32)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• 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 (EAS) allele frequency at 95% confidence interval = 0.308 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRGUK	NM_144648.3	MANE Select	c.939+3889C>G		intron	N/A	NP_653249.1
	LRGUK	NM_001365700.3		c.939+3889C>G		intron	N/A	NP_001352629.1
	LRGUK	NM_001365701.3		c.939+3889C>G		intron	N/A	NP_001352630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRGUK	ENST00000285928.3	TSL:1 MANE Select	c.939+3889C>G		intron	N/A	ENSP00000285928.2
	LRGUK	ENST00000695542.2		c.939+3889C>G		intron	N/A	ENSP00000511999.1
	LRGUK	ENST00000645682.1		c.939+3889C>G		intron	N/A	ENSP00000495637.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20024 AN: 152112 Hom.: 1669 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.132 AC: 20069 AN: 152230 Hom.: 1679 Cov.: 32 AF XY: 0.132 AC XY: 9855 AN XY: 74438

African (AFR) AF: 0.174 AC: 7242 AN: 41524

American (AMR) AF: 0.161 AC: 2465 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1661 AN: 5170

South Asian (SAS) AF: 0.173 AC: 835 AN: 4818

European-Finnish (FIN) AF: 0.0596 AC: 633 AN: 10612

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6329 AN: 68016

Other (OTH) AF: 0.143 AC: 301 AN: 2112

Alfa AF: 0.112 Hom.: 144

Bravo AF: 0.144

Asia WGS AF: 0.235 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.36
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: rs892984; hg19: chr7-133852181;