7-134249445-G-A

Position:

• chr7-134249445-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000285928.3(LRGUK):​c.2198+369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,016 control chromosomes in the GnomAD database, including 4,955 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 (4955 hom., cov: 32)
• Consequence: LRGUK ENST00000285928.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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

Verdict is Benign. Variant got -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 = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.2198+369G>A		intron_variant		ENST00000285928.3	NP_653249.1
LRGUK	XM_024446659.2	c.2198+369G>A		intron_variant			XP_024302427.1
LRGUK	XM_024446661.2	c.2198+369G>A		intron_variant			XP_024302429.1
LRGUK	XM_047419890.1	c.1991+369G>A		intron_variant			XP_047275846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.2198+369G>A		intron_variant		1	NM_144648.3	ENSP00000285928	P2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35233 AN: 151898 Hom.: 4951 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.232 AC: 35237 AN: 152016 Hom.: 4955 Cov.: 32 AF XY: 0.233 AC XY: 17272 AN XY: 74288

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.247

Alfa AF: 0.269 Hom.: 4358

Bravo AF: 0.210

Asia WGS AF: 0.129 AC: 448 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	0.14
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs1450890; hg19: chr7-133934197;