chr7-134152547-C-T

Variant names:

• chr7-134152547-C-T
• rs6953590
• NM_144648.3:c.670+4228C>T

Variant summary

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

The NM_144648.3(LRGUK):​c.670+4228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,020 control chromosomes in the GnomAD database, including 44,479 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 0.76 (44479 hom., cov: 33)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.670+4228C>T		intron_variant	Intron 5 of 19	ENST00000285928.3	NP_653249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.670+4228C>T		intron_variant	Intron 5 of 19	1	NM_144648.3	ENSP00000285928.2
LRGUK	ENST00000695542.2	c.670+4228C>T		intron_variant	Intron 5 of 15			ENSP00000511999.1
LRGUK	ENST00000645682.1	c.670+4228C>T		intron_variant	Intron 5 of 15			ENSP00000495637.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115205 AN: 151902 Hom.: 44421 Cov.: 33

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.759 AC: 115324 AN: 152020 Hom.: 44479 Cov.: 33 AF XY: 0.761 AC XY: 56523 AN XY: 74312

African (AFR) AF: 0.886 AC: 36792 AN: 41528

American (AMR) AF: 0.764 AC: 11669 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3468

East Asian (EAS) AF: 0.809 AC: 4198 AN: 5190

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4818

European-Finnish (FIN) AF: 0.780 AC: 8256 AN: 10586

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46482 AN: 67846

Other (OTH) AF: 0.753 AC: 1588 AN: 2108

Alfa AF: 0.735 Hom.: 5176

Bravo AF: 0.767

Asia WGS AF: 0.767 AC: 2660 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.72
PhyloP100		-1.5
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: rs6953590; hg19: chr7-133837300;