chr7-134231008-T-C

Variant names:

• chr7-134231008-T-C
• rs1222430
• NM_144648.3:c.1983+9090T>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+9090T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,148 control chromosomes in the GnomAD database, including 3,918 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 0.19 (3918 hom., cov: 32)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.1983+9090T>C		intron_variant	Intron 16 of 19	ENST00000285928.3	NP_653249.1
LRGUK	XM_024446659.2	c.1983+9090T>C		intron_variant	Intron 16 of 19		XP_024302427.1
LRGUK	XM_024446661.2	c.1983+9090T>C		intron_variant	Intron 16 of 19		XP_024302429.1
LRGUK	XM_047419890.1	c.1776+9090T>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+9090T>C		intron_variant	Intron 16 of 19	1	NM_144648.3	ENSP00000285928.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28386 AN: 152030 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.187 AC: 28478 AN: 152148 Hom.: 3918 Cov.: 32 AF XY: 0.188 AC XY: 13959 AN XY: 74366

African (AFR) AF: 0.328 AC: 13594 AN: 41480

American (AMR) AF: 0.206 AC: 3144 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2807 AN: 5156

South Asian (SAS) AF: 0.196 AC: 945 AN: 4812

European-Finnish (FIN) AF: 0.0702 AC: 744 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6156 AN: 68030

Other (OTH) AF: 0.181 AC: 381 AN: 2102

Alfa AF: 0.128 Hom.: 7501

Bravo AF: 0.209

Asia WGS AF: 0.333 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-0.71
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: rs1222430; hg19: chr7-133915760;